Search CTL/CD8+ T-Cell Epitope Database

Found 136 matching records:

Displaying record number 57523

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(A*0201)
Immunogen	in vitro stimulation or selection
Experimental methods	Tetramer binding
Keywords

Notes

The study investigated the effect of blocking interleukin-10 (IL-10) on HIV-specific CTL responses. PBMCs from viremic and aviremic patients were stimulated with optimal HIV epitopes in the presence of IL-10 receptor antibody. Blocking the receptor increased the number of HIV-specific CTLs, and the effect was higher in viremic than in aviremic patients.
This epitope was one of 12 known optimal epitopes used to stimulate PBMC from viremic and aviremic patients in order to test the effect of blocking IL-10.

References

Brockman2009 Mark A. Brockman, Douglas S. Kwon, Daniel P. Tighe, David F. Pavlik, Pamela C. Rosato, Jennifer Sela, Filippos Porichis, Sylvie Le Gall, Michael T. Waring, Kristin Moss, Heiko Jessen, Florencia Pereyra, Daniel G. Kavanagh, Bruce D. Walker, and Daniel E. Kaufmann. IL-10 Is Up-Regulated in Multiple Cell Types During Viremic HIV Infection and Reversibly Inhibits Virus-Specific T Cells. Blood, 114(2):346-356, 9 Jul 2009. PubMed ID: 19365081. Show all entries for this paper.

Displaying record number 57132

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	(B4801, B5703)
Immunogen	HIV-1 infection
Experimental methods	Intracellular cytokine staining, Relative replication capacity assay
Keywords	escape, HLA associated polymorphism

Notes

The frequency of known escape mutations was studied in 9 large cohorts from around the world. The frequencies of specific epitope escape variants were consistently correlated with the prevalence of the restricting HLA allele in each population, demonstrating strong evidence of viral adaptation to HLA on a population level.
The frequency of KAFSPEVIPMF escape variant A163X was correlated with the prevalence of B*5703. Despite a 0% prevalence of B*57 in the Japanese cohort, the A146X variant was present in 38% of subjects, suggesting that some non-B*57 alleles may also drive selection of this variant. A strong association was found between A146X and HLA-B*4801.

References

Kawashima2009 Yuka Kawashima, Katja Pfafferott, John Frater, Philippa Matthews, Rebecca Payne, Marylyn Addo, Hiroyuki Gatanaga, Mamoru Fujiwara, Atsuko Hachiya, Hirokazu Koizumi, Nozomi Kuse, Shinichi Oka, Anna Duda, Andrew Prendergast, Hayley Crawford, Alasdair Leslie, Zabrina Brumme, Chanson Brumme, Todd Allen, Christian Brander, Richard Kaslow, James Tang, Eric Hunter, Susan Allen, Joseph Mulenga, Songee Branch, Tim Roach, Mina John, Simon Mallal, Anthony Ogwu, Roger Shapiro, Julia G. Prado, Sarah Fidler, Jonathan Weber, Oliver G. Pybus, Paul Klenerman, Thumbi Ndung'u, Rodney Phillips, David Heckerman, P. Richard Harrigan, Bruce D. Walker, Masafumi Takiguchi, and Philip Goulder. Adaptation of HIV-1 to Human Leukocyte Antigen Class I. Nature, 458(7238):641-645, 2 Apr 2009. PubMed ID: 19242411. Show all entries for this paper.

Displaying record number 58494

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Canada
Experimental methods	Other
Keywords	characterizing CD8+ T cells, elite controllers

Notes

Dual color EliSpot testing for IL-2 and IFN-γ was used to determine whether CTL restricted by MHC Class I alleles associated with slow progression to disease, viz. B*57 and B*27, had a more poly-functional profile than other CD8+ cells in a treatment-naive cohort from Montreal. B*57/B*27-restricted CTL producing IL-2 or IFN-γ or IL-2/IFN-γ, were similar in both slow progressors (SP) and progressors. Other non-protective MHC-I-restricted CTL producing both IL-2/IFN-γ, were greater in number in SP than progressors.
Within SP, peptides restricted by both protective and non-protective MHC-I alleles elicited CTL with the same functional profile. For progressors, peptides and epitopes restricted by protective B*57/B*27 alleles stimulated a higher proportion of dual-(IL-2/IFN-γ)secreting CTL.
HLA-B*57-restricted Gag optimal epitope KAFSPEVIPMF was tested in a dual color EliSpot and found to elicit CTL that could produce IL-2 and/or IFN-γ.

References

Peretz2011 Yoav Peretz, Olivia Marra, Réjean Thomas, Danielle Legault, Pierre Côté, Mohamed-Rachid Boulassel, Danielle Rouleau, Jean-Pierre Routy, Rafick-Pierre Sékaly, Christos M Tsoukas, Cécile Tremblay, and Nicole F. Bernard. Relative Contribution of HIV-Specific Functional Lymphocyte Subsets Restricted by Protective and Non-Protective HLA Alleles. Viral Immunol, 24(3):189-198, Jun 2011. PubMed ID: 21668360. Show all entries for this paper.

Displaying record number 54793

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication
Keywords	class I down-regulation by Nef

Notes

The impact of Nef on antiviral activity was studied. CTL-targeting epitopes were susceptible to the effects of Nef, both in late (Gag, RT, Env) and in early proteins (Rev, Nef), although to a lesser degree in early proteins. HLA-C-restricted CTLs (unlike HLA-A and HLA-B) were unaffected by Nef both in early (Nef) and late (Env) proteins.
Late protein Gag epitope KAFSPEVIPMF-recognizing CTLs were less affected by Nef.

References

Adnan2006 Sama Adnan, Arumugam Balamurugan, Alicja Trocha, Michael S. Bennett, Hwee L. Ng, Ayub Ali, Christian Brander, and Otto O. Yang. Nef Interference with HIV-1-Specific CTL Antiviral Activity Is Epitope Specific. Blood, 108(10):3414-3419, 15 Nov 2006. PubMed ID: 16882705. Show all entries for this paper.

Displaying record number 58357

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	B57 KF11
Subtype	B, C
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection, in vitro stimulation or selection, vaccine
Country	South Africa, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining, Tetramer binding
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5)
Vaccine strain	B clade, C clade
Vaccine component	Gag

Notes

To increase coverage of functional epitopes across clades and to elicit cross-clade recognition, mosaic antigens comprising HIV Gag sequences from clades B and C were used to construct a bivalent mosaic vaccine. This was tested for recognition by Gag epitope-specific CTL, thereby comparing and confirming the processing, presentation and antigenicity of synthetic epitopes to natural ones. All 8 clade B epitopes tested in 12 US subjects as well as all 5 clade C epitopes tested in 10 South African subjects were expressed, stimulated CTL cytokine production and induced specific helper CD4 T cell responses. Mosaic-antigens however, elicited greater cross-clade recognition than natural antigens.
Epitope-KAFSPEVIPMF containing peptides, KVVEEKAFSPEVIPMFSALSE for Clade B and KVIEEKAFSPEVIPMFTALSE for Clade C were successfully used for detection of immune responses.

References

Ndhlovu2011 Zaza M. Ndhlovu, Alicja Piechocka-Trocha, Seanna Vine, Ashley McMullen, Kegakilwe C. Koofhethile, Phillip J. R. Goulder, Thumbi Ndung'u, Dan H. Barouch, and Bruce D. Walker. Mosaic HIV-1 Gag Antigens Can Be Processed and Presented to Human HIV-Specific CD8+ T Cells. J. Immunol., 186(12):6914-6924, 15 Jun 2011. PubMed ID: 21576505. Show all entries for this paper.

Displaying record number 58282

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining, Tetramer binding
Keywords	variant cross-reactivity, characterizing CD8+ T cells

Notes

To discover a correlation between HIV-1-specific CTL repertoires and CTL clone phenotype and function, CTL specific for HIV epitopes from chronic HIV-1 ART-free subjects were evaluated for expression of markers PD-1 (programmed death-1) and IL-7Ralpha (CD127), MHC I tetramer binding, cytokine production, and proliferation profiles of the dominant and subdominant clones. Dominant clonotypes had a stably higher PD-1 and lower CD127 expression, a stronger TCR avidity, failed to survive in culture at low stimulating peptide concentrations and had a lower capacity for cross-recognition. Subdominant clonotypes, however, produced higher cytokine levels in presence of variant epitope peptides, displayed greater cross-recognition and may therefore have a greater capacity to suppress viral replication of variants.
Epitope KF11 was recognized by TRBV clonotypes of patients 10004, 10027, 10040, 10070, 10071, 10076 and 20018. In longitudinal studies, the KF11-specific dominant TRBV5 population of cells maintained high PD-1 expression in comparison to the subdominant TRBV7 clonotype.

References

Conrad2011 Joseph A. Conrad, Ramesh K. Ramalingam, Rita M. Smith, Louise Barnett, Shelly L. Lorey, Jie Wei, Brenna C. Simons, Shanmugalakshmi Sadagopal, Dirk Meyer-Olson, and Spyros A. Kalams. Dominant Clonotypes within HIV-Specific T Cell Responses Are Programmed Death-1 High and CD127 Low and Display Reduced Variant Cross-Reactivity. J. Immunol., 186(12):6871-6885, 15 Jun 2011. PubMed ID: 21562156. Show all entries for this paper.

Displaying record number 54271

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape

Notes

Impact of CTL escape mutations in HLA-B57 positive elite supressors was examined. Escape mutations in B57-restricted Gag epitopes were present in all viruses derived from plasma but were lacking in proviruses, suggesting a strong selective pressure acting upon virus in plasma. IFN-gamma responses were detected to both wild-type epitopes and mutant plasma virus epitopes. In some individuals, CD8 IL-2 secretion, rather than IFN-gamma responses, showed better correlation with the plasma viral variants.
A163S mutation in this epitope can potentially act as a CTL escape mutation.

References

Bailey2006 Justin R. Bailey, Thomas M. Williams, Robert F. Siliciano, and Joel N. Blankson. Maintenance of Viral Suppression in HIV-1-Infected HLA-B*57+ Elite Suppressors Despite CTL Escape Mutations. J. Exp. Med., 203(5):1357-1369, 15 May 2006. PubMed ID: 16682496. Show all entries for this paper.

Displaying record number 58741

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172 NL4-3)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining
Keywords	elite controllers

Notes

In order to dissect whether natural control of HIV-1 infection is due to infection with a defective virus or whether it is due to host factors, 2 transmission pairs were studied and compared to an elite suppressor transmission pair with defective virus. The transmission pairs under study were Pair 1 = a male chronic progressor (CP1) and a female viremic controller (VC1); Pair 2 = a male chronic progressor (CP2) and female elite suppressor (ES38). Viral replication from CP1/VC1 and CP2/ES38 pairs was efficient, all patients had two wt CCR5 alleles, no homozygous protective HLA-C single nucleotide polymorphism (SNP) was found, none were positive for the KIR3DS1-activating allele, but ES38 is protective allele HLA-B*5703 positive.
For the CP1/VC1 pair, it was found that VC1 had a higher percentage of CD4+ T cells that coexpressed γ-IFN and IL-2 secretions as well as CTL that coexpressed more perforin and TNF-α than CP1. CTL from VC1 substantially reduced infected CD4+ T cells in a suppression assay while CTL from CP1 had no effect.
Epitope KF11, KAFSPEVIPMF, is restricted by protective HLA-B*57 and was targeted by ES38 as seen by EliSpot.

References

Buckheit2012 Robert W. Buckheit, III, Tracy G. Allen, Angela Alme, Maria Salgado, Karen A. O'Connell, Sarah Huculak, Oluwaseun Falade-Nwulia, Thomas M. Williams, Joel E. Gallant, Robert F. Siliciano, and Joel N. Blankson. Host Factors Dictate Control of Viral Replication in Two HIV-1 Controller/Chronic Progressor Transmission Pairs. Nat Commun, 3:716, 2012. PubMed ID: 22395607. Show all entries for this paper.

Displaying record number 61240

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, TCR usage

Notes

Recent findings of the HIV-specific TCR repertoire are reviewed here. KAFSPEVIPMF (KF11)-TCR repertoire are diverse and flexible and TCR gene usage is biased.

References

Lissina2016 Anna Lissina, Lisa A. Chakrabarti, Masafumi Takiguchi, and Victor Appay. TCR Clonotypes: Molecular Determinants of T-Cell Efficacy against HIV. Curr. Opin. Virol., 16:77-85, Feb 2016. PubMed ID: 26874617. Show all entries for this paper.

Displaying record number 59132

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40 NL4.3)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infected monocyte-derived, HIV-1 infection
Country	United States
Experimental methods	Chromium-release assay, Other
Keywords	epitope processing, dendritic cells

Notes

Variations in HIV-1 peptide degradation pattern, kinetics, as well as production and degradation of HIV epitopes were correlated with cytosolic antigen-processing machinery of either monocyte-derived dendritic cells (DCs) or macrophages (MPs) after maturation with TRL4, TLR7/8 ligands. Generation of epitope precursors and epitopes from epitope-containing peptides was dependent on specific epitope and cytosolic extract type, leading to a 2- to 25-fold difference in CTL response in DCs, MPs and monocytes.
Intracellular stability of epitopes is epitope-dependent, with stability rankings being TW10>RK9>ATK9>KF11>ISW9. B*57-restricted KAFSPEVIPMF, KF11, was fairly stable in iDCs (t_1/2=22.1') and in iMPs (t_1/2=20.4').

References

Dinter2014 Jens Dinter, Pauline Gourdain, Nicole Y. Lai, Ellen Duong, Edith Bracho-Sanchez, Marijana Rucevic, Paul H. Liebesny, Yang Xu, Mariko Shimada, Musie Ghebremichael, Daniel G. Kavanagh, and Sylvie Le Gall. Different Antigen-Processing Activities in Dendritic Cells, Macrophages, and Monocytes Lead to Uneven Production of HIV Epitopes and Affect CTL Recognition. J. Immunol., 193(9):4322-4334, 1 Nov 2014. PubMed ID: 25230751. Show all entries for this paper.

Displaying record number 53776

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	B, C
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding
Keywords	subtype comparisons, escape, viral fitness and reversion, optimal epitope

Notes

The authors correlate preservation of certain consensus epitope sequences with HLA-I (novel epitope KF9, KAAFDLSFF or KAAVDLSHF with B*57/5801; and LI9, LPPVVAKEI with B*51) as opposed to the usual correlation between variants from the consensus and HLA-I.
An escape mutation, A2G (KgFSPEVIPMF), is suggested to be a result of selection pressure from the HLA-B*57 allele, and can be transmitted and stable in the absence of HLA-B*57. Evidence indicated that the mechanism of escape was an increased off-rate.

References

Leslie2005a Alasdair Leslie, Daniel Kavanagh, Isobella Honeyborne, Katja Pfafferott, Charles Edwards, Tilly Pillay, Louise Hilton, Christina Thobakgale, Danni Ramduth, Rika Draenert, Sylvie Le Gall, Graz Luzzi, Anne Edwards, Christian Brander, Andrew K. Sewell, Sarah Moore, James Mullins, Corey Moore, Simon Mallal, Nina Bhardwaj, Karina Yusim, Rodney Phillips, Paul Klenerman, Bette Korber, Photini Kiepiela, Bruce Walker, and Philip Goulder. Transmission and Accumulation of CTL Escape Variants Drive Negative Associations between HIV Polymorphisms and HLA. J. Exp. Med., 201(6):891-902, 21 Mar 2005. PubMed ID: 15781581. Show all entries for this paper.

Displaying record number 58803

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	B*57-KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Other, Tetramer binding
Keywords

Notes

This study of post-ART TCR repertoire and clonal diversity was undertaken in 8 HIV-1 infected subjects using 14 HIV-specific CTL responses. It was noted that while circulating and memory CTL decreased along with a reduction in diversity of CTL responses, the overall hierarchy of TCR clonotypes was unchanged. A redistribution in memory phenotype did occur as well as decrease PD-1, CD38 expression, however PD-1 continued to be expressed more highly on dominant clonotypes. Therefore dominant clonotypes maintain their ability to recognize antigen post-ART, and TCR diversity also persists.
Both different clonotypes of epitope KF11 studied showed decreased numbers post-ART. Dominant clonotypes remained constant pre- and post-ART. Decreases in diversity of epitope-specificity of TCR were also seen pre- and post-ART in clonotypes.

References

Conrad2012 Joseph A. Conrad, Ramesh K. Ramalingam, Coley B. Duncan, Rita M. Smith, Jie Wei, Louise Barnett, Brenna C. Simons, Shelly L. Lorey, and Spyros A. Kalams. Antiretroviral Therapy Reduces the Magnitude and T Cell Receptor Repertoire Diversity of HIV-Specific T Cell Responses without Changing T Cell Clonotype Dominance. J. Virol., 86(8):4213-4221, Apr 2012. PubMed ID: 22258246. Show all entries for this paper.

Displaying record number 58767

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	Gag-KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Australia, Canada, United States
Experimental methods	Chromium-release assay
Keywords	class I down-regulation by Nef

Notes

Factors impacting Nef-mediated immune evasion were studied using 17 epitopes and the kinetics of infected cell clearance. Recognition and clearance of infected presenting cells by Gag-specific CTL is dependent upon the specific epitope it presents as well as virus inoculum (multiplicity of infection, moi), but not on the particular restricting HLA or on any kinetic advantage for early expressed proteins like Rev, Tat and Nef.
HLA-B*57-restricted Gag-KF11-specific CTL were not affected by Nef-mediated down-regulation of HLA as they efficiently lysed infected presenting cells, and they were viral inoculum concentration-dependent.

References

Chen2012 Diana Y. Chen, Arumugam Balamurugan, Hwee L. Ng, William G. Cumberland, and Otto O. Yang. Epitope Targeting and Viral Inoculum Are Determinants of Nef-Mediated Immune Evasion of HIV-1 from Cytotoxic T Lymphocytes. Blood, 120(1):100-111, 5 Jul 2012. PubMed ID: 22613796. Show all entries for this paper.

Displaying record number 1176

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

Study examines the effect of highly active antiretroviral therapy (HAART) on HIV-1 plasma viral load, CTLp and CTLe frequencies in 8 infected children.
CTLp (precursors) were measured by stimulating in culture and assaying using 51Cr release, against vaccina expressed IIIB Env, Gag, Pol, Nef, and CTLe were measured by ELISPOT.
CTL against B*57-KAFSPEVIPMF was a de novo response observed in one of the children when viral load increased as a result of stopping therapy.
HIV-1 specific CTL responses initially increased in children with complete viral suppression, but then decreased, suggesting viral replication is needed to maintain CTL responses.

References

Spiegel1999 H. M. Spiegel, E. DeFalcon, G. S. Ogg, M. Larsson, T. J. Beadle, P. Tao, A. J. McMichael, N. Bhardwaj, C. O'Callaghan, W. I. Cox, K. Krasinski, H. Pollack, W. Borkowsky, and D. F. Nixon. Changes in Frequency of HIV-1-Specific Cytotoxic T Cell Precursors and Circulating Effectors after Combination Antiretroviral Therapy in Children. J. Infect. Dis., 180:359-368, 1999. PubMed ID: 10395850. Show all entries for this paper.

Displaying record number 58004

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	in vitro stimulation or selection
Experimental methods	Chromium-release assay, Cytotoxicity assay, Other
Keywords	epitope processing

Notes

The cytosolic stability of 166 HIV-1 epitopes was found to be highly variable. Stability was correlated with antigenicity. Stability could be modulated through mutations, and some naturally-occurring mutations affect cytosolic stability and CTL recognition; reduced stability may be associated with escape.
B*57-KF11 was relatively unstable in uninfected PBMC. In a cytotoxicity assay, cells loaded with KF11 displayed limited lysis by epitope-specific CTLs.

References

Lazaro2011 Estibaliz Lazaro, Carl Kadie, Pamela Stamegna, Shao Chong Zhang, Pauline Gourdain, Nicole Y. Lai, Mei Zhang, Sergio A. Martinez, David Heckerman, and Sylvie Le Gall. Variable HIV Peptide Stability in Human Cytosol Is Critical to Epitope Presentation and Immune Escape. J. Clin. Invest., 121(6):2480-2492, Jun 2011. PubMed ID: 21555856. Show all entries for this paper.

Displaying record number 53123

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Spain
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Proliferation
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

Structured treatment interruption (STI) alone is not able to control viral replication in chronically infected patients, probably due to lack of strong, maintained T-helper cell responses. HIV-1 specific CD8+ T-cell responses were shown to increase significantly until the end of the follow up, but were not correlated with viral load.
7/7 patients recognized this epitope.

References

Plana2004 Montserrat Plana, Felipe Garcia, Annette Oxenius, Gabriel M. Ortiz, Anna Lopez, Anna Cruceta, Gabriel Mestre, Emilio Fumero, Catherine Fagard, Maria Antonia Sambeat, Ferran Segura, José M. Miró, Mireia Arnedo, L. Lopalcos, Tomas Pumarola, Bernard Hirschel, Rodney E. Phillips, Douglas F. Nixon, Teresa Gallart, and Jose M. Gatell. Relevance of HIV-1-Specific CD4+ Helper T-Cell Responses During Structured Treatment Interruptions in Patients With CD4+ T-Cell Nadir Above 400/mm3. J. Acquir. Immune Defic. Syndr., 36(3):791-799, 1 Jul 2004. PubMed ID: 15213562. Show all entries for this paper.

Displaying record number 59382

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
KAFSPEVIPMF had a significantly positive association with HLA B*57; it was recognized by 85/104 B*57-positive subjects and 18/237 B*57-negative subjects.
KAFSPEVIPMF was significantly protective, associated with viral control when restricted by HLA-B*57/*5801 in a cohort of 245 controllers and 96 progressors.

References

Pereyra2014 Florencia Pereyra, David Heckerman, Jonathan M. Carlson, Carl Kadie, Damien Z. Soghoian, Daniel Karel, Ariel Goldenthal, Oliver B. Davis, Charles E. DeZiel, Tienho Lin, Jian Peng, Alicja Piechocka, Mary Carrington, and Bruce D. Walker. HIV Control Is Mediated in Part by CD8+ T-Cell Targeting of Specific Epitopes. J. Virol., 88(22):12937-12948, Nov 2014. PubMed ID: 25165115. Show all entries for this paper.

Displaying record number 55112

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	characterizing CD8+ T cells

Notes

Maturation phenotypes of CTLs were compared between HIV-1 Controller and Progressor subjects. Controllers were found to recognize a median of 18 epitopes compared to 15 by Progressors. While Controllers certainly had higher frequencies of terminally differentiated effector CTLs (CD45RA+/CCR7-), Progressors had higher mean frequencies of CD45RA-/CCR7- effector memory, CD45RA-/CCR7+ central memory (statistically significant) and CD45RA+/CCR7+ naive CTLs. No correlation was seen between CTL effector phenotype and either HLA-type or epitope.
B*57-restricted epitope KAFSPEVIPMF does not correlate with any particular CTL maturation phenotype. No study subjects generated terminally differentiated CTLs against this epitope.

References

Addo2007 Marylyn M. Addo, Rika Draenert, Almas Rathod, Cori L. Verrill, Benjamin T. Davis, Rajesh T. Gandhi, Gregory K. Robbins, Nesli O. Basgoz, David R. Stone, Daniel E. Cohen, Mary N. Johnston, Theresa Flynn, Alysse G. Wurcel, Eric S. Rosenberg, Marcus Altfeld, and Bruce D. Walker. Fully Differentiated HIV-1 Specific CD8+ T Effector Cells Are More Frequently Detectable in Controlled than in Progressive HIV-1 Infection. PLoS ONE, 2(3):e321, 2007. PubMed ID: 17389912. Show all entries for this paper.

Displaying record number 59190

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40 NL4.3)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods	In vitro proteasome digestion, Other
Keywords	epitope processing

Notes

7 HIV protease inhibitors (PIs) were shown to alter not only proteasome but also aminopeptidase activities that generate epitopes for MHC presentation. These inhibitors altered degradation patterns, sensitivity of peptides to degradation, kinetics and amounts of epitope production and therefore recognition by CTLs.
Precursor to KF11, KAFSPEVIPMF, used with different PIs was B*57-restricted 3KF11, VIIKAFSPEVIPMF. Half life of KF11 was increased by Saquinavir and Ritonavir. KF11-specific CTL decreased kinetics and killing in the presence of Ritonavir, Saquinavir, Nelfinavir and Indinavir.

References

Kourjian2014 Georgio Kourjian, Yang Xu, Ijah Mondesire-Crump, Mariko Shimada, Pauline Gourdain, and Sylvie Le Gall. Sequence-Specific Alterations of Epitope Production by HIV Protease Inhibitors. J. Immunol., 192(8):3496-3506, 15 Apr 2014. PubMed ID: 24616479. Show all entries for this paper.

Displaying record number 59139

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	elite controllers

Notes

In a follow-up on the anonymous 1999 Berlin patient (not Timothy Brown of 2008), viral replication suppression was seen after 15 years of absence of ART. Half the HIV-specific CTL responses in this patient were restricted by HLA-B*57, with the most immunodominant being against Nef HW9, HTQGYFPDW.
Patient autologous sequence of B*57-restricted p24 KF11, KAFSPEVIPMF, elicited a CTL response of <500 sfu/10<sup>6</sup> PBMC when tested by EliSpot.

References

Jessen2014 Heiko Jessen, Todd M. Allen, and Hendrik Streeck. How a Single Patient Influenced HIV Research — 15-Year Follow-Up. N. Engl. J. Med., 370(7):682-683, 13 Feb 2014. PubMed ID: 24521131. Show all entries for this paper.

Displaying record number 55332

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	rate of progression, acute/early infection, memory cells

Notes

CD127 hi memory CTLs were correlated with different patient groups - subjects with chronic HIV-1 infection or controllers or those treated early with ART. For patients with chronic infection, CD127 hi CTL levels decrease greatly. Early ART treatment alone maintained these long-lived memory T cells.
In response to epitope KF11, KAFSPEVIPMF, IFN-gamma was produced by CD127 lo cells by both controllers and chronic patients. IL-2 and TNF-alpha were produced by both CD127 hi and lo cells in controllers. HLA-restriction was to -B*57.

References

Sabbaj2007 Steffanie Sabbaj, Sonya L. Heath, Anju Bansal, Sameera Vohra, J Michael Kilby, Allan J. Zajac, and Paul A. Goepfert. Functionally Competent Antigen-Specific CD127(hi) Memory CD8+ T Cells Are Preserved Only in HIV-Infected Individuals Receiving Early Treatment. J. Infect. Dis., 195(1):108-117, 1 Jan 2007. PubMed ID: 17152014. Show all entries for this paper.

Displaying record number 61562

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	B57-KF11(p24)
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Patient MHC/HLA	OP246: A01, A02, B51, B57, Cw06; P1004: A02, B08, B57, Cw06, Cw07; AC-43: A24, A31, B14, B57, Cw07, Cw08; AC-38: A01, A03, B07, B57, Cw06, Cw07; AC-108: A02, B57, B61, Cw03, Cw06; AC-109: A01, A02, B14, B57, Cw07, Cw*08
Country	Canada, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	acute/early infection, protective allele

Notes

HLA-B*57-restricted CTL responses were relatively immunodominant in breadth and strength during acute early infection of HIV-1. 6/9 HLA-B*57 patients controlled viremia to <5000 copies/ml for up to 29 months post-infection.
Epitope B57-KF11(p24), KAFSPEVIPMF, elicited CTL response in 6/9 acute early HIV-1-infected subjects; OP246 = 240 SFC/10⁶ PBMC, AC-43 = 400 SFC/10⁶ PBMC, AC-38 = 60 SFC/10⁶ PBMC, AC-109 = 520 SFC/10⁶ PBMC, AC-108 = 700 SFC/10⁶ PBMC, and P1004 = 60 SFC/10⁶ PBMC.

References

Altfeld2003a Marcus Altfeld, Marylyn M. Addo, Eric S. Rosenberg, Frederick M. Hecht, Paul K. Lee, Martin Vogel, Xu G. Yu, Rika Draenert, Mary N. Johnston, Daryld Strick, Todd M. Allen, Margaret E. Feeney, James O. Kahn, Rafick P. Sekaly, Jay A. Levy, Jürgen K. Rockstroh, Philip J. Goulder, and Bruce D. Walker. Influence of HLA-B57 on Clinical Presentation and Viral Control during Acute HIV-1 Infection. AIDS, 17(18):2581-2591, 5 Dec 2003. PubMed ID: 14685052. Show all entries for this paper.

Displaying record number 55768

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, elite controllers

Notes

This is the first documentation of transmission of HIV-1 from a patient who developed AIDS (Progressor) to an Elite Suppresssor (ES).
Both patients are HLA-B*5703-positive. The ES also has B*27 allele. Escape mutations in HLA-B*57-restricted epitopes were present in both patients, suggesting that they by themselves cannot explain the difference in the outcomes.
The study concluded that viral replication is controlled in ES by at least two mechanisms: (i) direct inhibition of viral replication by polyfunctional HIV-1 specific CD8+ T cells that proliferate in response to autologous viral peptides; (ii) selection for and maintenance of escape mutations that have a negative impact on viral fitness.
In this epitope, the ES had A163S substitution (KsFSPEVIPMF), which is very rare in B clade isolates, and the Progressor had A163N substitution (KnFSPEVIPMF). A163S substitution did not significantly affect viral replication, as shown using the pseudotype virus.

References

Bailey2008 Justin R. Bailey, Karen O'Connell, Hung-Chih Yang, Yefei Han, Jie Xu, Benjamin Jilek, Thomas M. Williams, Stuart C. Ray, Robert F. Siliciano, and Joel N. Blankson. Transmission of Human Immunodeficiency Virus Type 1 from a Patient Who Developed AIDS to an Elite Suppressor. J. Virol., 82(15):7395-7410, Aug 2008. PubMed ID: 18495769. Show all entries for this paper.

Displaying record number 59028

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection, vaccine
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	vaccine-induced immune responses, therapeutic vaccine

Vaccine Details

Vaccine type	DNA prime with Ad5 boost
Vaccine strain	A clade, B clade, C clade
Vaccine component	Env, Gag, Nef, Pol

Notes

This study investigated the efficacy of a therapeutic vaccine designed to boost CTLs and/or induce new CTL responses in HIV-infected individuals. The vaccine differed from other therapeutic vaccines that were previously studied in that it included not only clade B Gag, Pol, and Nef but also Env proteins from multiple clades (A, B, and C) and was followed by a replication-deficient adenovirus type 5 boost. 17 HIV-infected subjects were randomly assigned in a 2:1 ratio to receive vaccine or placebo. While vaccinated individuals exhibited as significantly stronger, polyfunctional CTL response and broadened epitope-specific CTL repertoire, no changes were observed in frequency of latent infection or single-copy viral load.
The epitope that stimulated the largest increase in CTL response was Clade A YI9, YPPIQGVI. All other epitopes elicited an unchanged or only slightly activated response.
KF11, KAFSPEVIPMF, was one of 9/48 vaccine-matched epitopes that were functionally tested. These epitopes were identified in vaccine recipients by apheresis followed by CTL epitope mapping. Gag-specific responses were found to be most increased by vaccination. KF11 CTL clones were boosted in number post-vaccination.

References

Casazza2013 Joseph P. Casazza, Kathryn A. Bowman, Selorm Adzaku, Emily C. Smith, Mary E. Enama, Robert T. Bailer, David A. Price, Emma Gostick, Ingelise J. Gordon, David R. Ambrozak, Martha C. Nason, Mario Roederer, Charla A. Andrews, Frank M. Maldarelli, Ann Wiegand, Mary F. Kearney, Deborah Persaud, Carrie Ziemniak, Raphael Gottardo, Julie E. Ledgerwood, Barney S. Graham, Richard A. Koup, and VRC 101 Study Team. Therapeutic Vaccination Expands and Improves the Function of the HIV-Specific Memory T-Cell Repertoire. J. Infect. Dis., 207(12):1829-1840, 15 Jun 2013. PubMed ID: 23482645. Show all entries for this paper.

Displaying record number 62010

HXB2 Location	Gag(162-172) p24(30-40)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	B*57-KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	binding affinity, structure, assay or method development, contact residues

Notes

Genome-wide association studies (GWAS) are used in a novel method of predicting residues in conserved epitopes with a high mutation cost to HIV fitness that are best targeted by a vaccine. Protein structure-based network analysis was used to quantify the topological importance of each residue to the tertiary and quaternary structure of HIV p24 protein as residue-residue interactions. A network score was generated for each residue (node) using data on non-covalent interactions (edges) - van der Waals interactions, hydrogen bonds, salt bridges, disulfide bonds, π-π interactions, π-cation interactions, metal-coordinated bonds and local hydrophobic packing. Residues of low-mutation tolerance were at important network positions and impaired viral replication fitness greatly. These residues were found in highly networked epitopes that were presented more often by protective HLA. Natural controllers of infection targeted more of these highly networked CTL epitopes, even in the absence of protective presenting HLA alleles.
Comparison within 5,430 Clade B isolates showed an inverse relationship between network score and mutational frequency in 11 additional HIV proteins. Gag p24 was the most highly networked protein due to extensive capsid multimerization requirements, making it mutationally fragile and linking Gag-specific CTL breadth with lower VL.
Experimental mutation of highly networked residues resulted in impairment of HIV infectivity at 2 days and viral replication at 7 days but mutation of residues with poor network scores was not impactful.
Risk versus Protective HLA alleles were able to be delineated by averaging residue network scores involved in HLA binding, TCR recognition, and peptide processing of an epitope associated with that HLA allele. Protective vs. non-protective HLA of controllers, however, had no significant difference in their eptiopes' network scores.
Neutral-HLA-restricted immunodominant epitopes of controller subjects contained much more highly networked residues than progressor subjects'. Controllers and progressors with similar CTL proliferation also had a significant difference in the sum of network scores of targeted epitopes.
Protective epitope, B*57-KF11 contains highly networked residues that bridge the N- and C- terminal domains of Gag p24 and that contact HLA anchor and TCR sites. While A31 and F40 are HLA anchor residues, the rest of the residues - F32, S33, P34, E35, V36, I37, P38, M39 - contact TCR. It has a normalized network score of 8.78 and is presented by B*5701, B*5703 or B63.
Supplementary Table S3 contains 260 Epitope Network Scores of HIV optimal CTL epitopes, pp. 25-27, http://science.sciencemag.org/content/suppl/2019/05/01/364.6439.480.DC1.

References

Gaiha2019 Gaurav D. Gaiha, Elizabeth J. Rossin, Jonathan Urbach, Christian Landeros, David R. Collins, Chioma Nwonu, Itai Muzhingi, Melis N. Anahtar, Olivia M. Waring, Alicja Piechocka-Trocha, Michael Waring, Daniel P. Worrall, Musie S. Ghebremichael, Ruchi M. Newman, Karen A. Power, Todd M. Allen, James Chodosh, and Bruce D. Walker. Structural Topology Defines Protective CD8+ T Cell Epitopes in the HIV Proteome. Science, 364(6439):480-484, 3 May 2019. PubMed ID: 31048489. Show all entries for this paper.

Displaying record number 56342

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(16-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B, C
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Canada, South Africa
Experimental methods
Keywords	escape

Notes

A statistical model, the phylogenetic dependency network (PDN), was developed to differentiate the confounding effects of codon variation, linkage disequilibrium of HLA alleles and HIV phylogeny from HLA-associated evolution including HIV selection by HLA-pressure and codon evolution.
This approach was applied to 2 cohorts of 1144 Gag sequences from HIV-infected individuals, generating associations between HIV codons themselves and codons with HLA alleles. Results generated predicted escapes that confirmed that escape kinetics and compensating mutations are consistent across clades. General patterns of covariation and CTL adaptation were determined. Some clade-based differences were identified.
HLA-B*57-restricted KAFSPEVIPMF escape, A163G i.e. KgFSPEVIPMF is predicted by escape substitutions in other epitopes, viz. T242N in TW10, I147M in IW9 and lack of escape at 310 in QW9.

References

Carlson2008 Jonathan M. Carlson, Zabrina L. Brumme, Christine M. Rousseau, Chanson J. Brumme, Philippa Matthews, Carl Kadie, James I. Mullins, Bruce D. Walker, P. Richard Harrigan, Philip J. R. Goulder, and David Heckerman. Phylogenetic Dependency Networks: Inferring Patterns of CTL Escape and Codon Covariation in HIV-1 Gag. PLoS Comput Biol, 4(11):e1000225, Nov 2008. PubMed ID: 19023406. Show all entries for this paper.

Displaying record number 56377

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
Escape (and reversion) rates for B*57-restricted epitopes were highest for Gag-TW10 (TSTLQEQIGW) > RT-IW9 (IVLPEKDSW) > Nef-YY9 (YTPGPGIRY) > Nef-HW9 (HTQGYFPDW) > Gag-IW9 (ISPRTLNAW) > Gag-KF11 (KAFSPEVIPMF) .
HLA-B*57-associated substitution within optimally defined epitope KAFSPEVIPMF is at position A2, KaFSPEVIPMF. Despite >40% frequency of recognition in acute infection, KF11 exhibited no HLA-driven sequence evolution.

References

Brumme2008 Zabrina L. Brumme, Chanson J. Brumme, Jonathan Carlson, Hendrik Streeck, Mina John, Quentin Eichbaum, Brian L Block, Brett Baker, Carl Kadie, Martin Markowitz, Heiko Jessen, Anthony D. Kelleher, Eric Rosenberg, John Kaldor, Yuko Yuki, Mary Carrington, Todd M. Allen, Simon Mallal, Marcus Altfeld, David Heckerman, and Bruce D. Walker. Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute/Early HIV-1 Infection. J. Virol., 82(18):9216-9227, Sep 2008. PubMed ID: 18614631. Show all entries for this paper.

Displaying record number 58971

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172 NL4-3)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	in vitro stimulation or selection
Experimental methods	CTL suppression of replication, In vitro proteasome digestion, Other
Keywords	epitope processing, class I down-regulation by Nef, kinetics

Notes

CTL-mediated suppression of replication and Nef-mediated HLA-I down regulation were determined for HIV-1 that had a translocation of specific Gag epitopes to the Nef gene versus an index HIV-1 (the endogenous version of the epitope that was translocated was mutated, ablating its function). Early Gag epitope presentation kinetics were found to have different outcomes based on which of three epitopes, SL9, SLYNTVATL, KF11, KAFSPEVIPMF, or TW10, TSTLQEQIGW, were translocated and which endogenous Nef epitopes they disrupted. Processing assays to follow presentation of each of the above epitopes showed that TW10 was most inefficiently generated.
All translocations to the N-terminal of Nef did not disrupt Nef's ability to down regulate HLA-1 as had previously been seen in translocations to the C-terminal of Nef.
Epitope presentation kinetics were thus shown to be critical in antiviral efficiency. In addition epitope context could be key in kinetics of epitope presentation. At early stages, Gag epitopes are not uniformly presented, as presentation is epitope and context-related.
KF11, KAFSPEVIPMF-specific CTLs are normally Nef-insensitive and disruption of Nef with this epitope did not change that, or enhance their anti-HIV activity.

References

Balamurugan2013 Arumugam Balamurugan, Ayub Ali, Julie Boucau, Sylvie Le Gall, Hwee L. Ng, and Otto O. Yang. HIV-1 Gag Cytotoxic T Lymphocyte Epitopes Vary in Presentation Kinetics Relative to HLA Class I Downregulation. J. Virol., 87(15):8726-8734, Aug 2013. PubMed ID: 23740989. Show all entries for this paper.

Displaying record number 62109

HXB2 Location	Gag(162-172) p24(30-40)	Gag Epitope Map
Author Location	p24(162-172 NL4-3)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B*57)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	vaccine antigen design, viral fitness and reversion

Notes

Computational models were used to translate published HIV-1 sequence data into quantitative viral fitness landscapes with peaks and valleys, that are a function of the amino acid sequences of its constituent proteins. In this case, Clade B Gag was modeled. Predictions were tested against in vitro fitness measurements and were consistent.
Epitope KAFSPEVIPMF is used as an example from Brockman2010 [Brockman et al. J.Virol. 84:11937-49] where each amino acid position within the epitope is associated with a different energy cost, ΔE, and the greater the cost the higher the fitness penalty. Observed HLA-associated escape position at A163 however was one of the positions with the highest h_i value, i.e. the most energetically costly to change.
Based on fitness costs, the authors created a rank-ordered bar chart called the "Epitope Index" and marked out immunodominant response associations on it. The epitope index reads Gag: (164-172)-B*57; (162-172)-B*57 i.e. KF11; (167-175)-A*26; (260-267)-B*08; (240-249)-B*57 i.e. TW10; (296-306)-B*14; (147-155)-B*57; (349-359)-A*11; (263-272)-B*27; (269-277)-B*15; (145-155)-A*25; (306-316)-B*44, from highest to lowest fitness costs.
Brumme2009 is not annotated in this database as epitopes were not immunologically defined, but the table of polymorphisms is available at https://www.hiv.lanl.gov/content/immunology/pdf/2010/escape_article_supplement.html. and a review of the work is available on the main page, hiv.lanl.gov under 'Tools and Data Sets', "Identifying HLA-Associated Polymorphisms in HIV-1" (PDF).

References

Ferguson2013a Andrew L. Ferguson, Jaclyn K. Mann, Saleha Omarjee, Thumbi Ndung'u, Bruce D Walker, and Arup K. Chakraborty. Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design. Immunity, 38(3):606-617, 21 Mar 2013. PubMed ID: 23521886. Show all entries for this paper.

Displaying record number 56754

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The study analyzed the kinetics of the HIV-specific CD8+ T-cell response in 21 acutely infected subjects. The first responses peaked at as early as 5 days, but were of limited epitope breadth. Responses of additional specificities expanded in subsequent waves, resulting in successive shifts in epitope immunodominance over time. The results document the preferential expansion of CD8+ T cells recognizing a subset of epitopes in acute infection and suggest that the initial T-cell response may influence the efficiency of viral containment in early infection.
KAFSPEVIPMF is an optimally-defined epitope targeted by the first-analyzed T-cell responses in acute infection.

References

Turnbull2009 Emma L. Turnbull, MaiLee Wong, Shuyi Wang, Xiping Wei, Nicola A. Jones, Karen E. Conrod, Diana Aldam, Jo Turner, Pierre Pellegrino, Brandon F. Keele, Ian Williams, George M. Shaw, and Persephone Borrow. Kinetics of Expansion of Epitope-Specific T Cell Responses During primary HIV-1 Infection. J. Immunol., 182(11):7131-7145, 1 Jun 2009. PubMed ID: 19454710. Show all entries for this paper.

Displaying record number 57247

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Barbados, Haiti, Jamaica
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	mother-to-infant transmission, elite controllers

Notes

To dissect whether the protective effect of HLA-B*57 in HIV-1 infection is due to CTL that recognize HLA-B*57-restricted epitopes or by the presence of viral-fitness attenuating mutations in such B*57 epitopes, 13 mother-infant pairs were studied. The B57 advantage is primarily through the maintenance of a fitness-attenuating mutation in p24-Gag, T242N in epitope TW10 (TSTLQEQIGW).
Regardless of parental inheritance, HLA-B57 controls VL even in infancy and even when escape mutations from B*57 positive mothers are transmitted. Mutations in p24-Gag are predominant in mismatched-HLA subject pairs and arise after vertical transmission, impacting viral fitness.
Epitope KF11, KAFSPEVIPMF, rarely escapes in Clade B and no stable mutation was seen in these subject pairs. The A163G mutation, KgFSPEVIPMF, likely affects viral fitness. Other variants seen were KsFSPEVIPMF, KnFSPEVIPMF, KgFnPEVIPMF and KqFSPEVIPMF. 3 of 4 infants with paternally inherited B57 and 2 of 4 with maternally inherited B57 recognized this epitope.

References

Schneidewind2009 Arne Schneidewind, Yanhua Tang, Mark A. Brockman, Elizabeth G. Ryland, Jacqueline Dunkley-Thompson, Julianne C. Steel-Duncan, M. Anne St. John, Joseph A. Conrad, Spyros A. Kalams, Francine Noel, Todd M. Allen, Celia D. Christie, and Margaret E. Feeney. Maternal Transmission of Human Immunodeficiency Virus Escape Mutations Subverts HLA-B57 Immunodominance but Facilitates Viral Control in the Haploidentical Infant. J. Virol., 83(17):8616-8627, Sep 2009. PubMed ID: 19515764. Show all entries for this paper.

Displaying record number 57259

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	A1, D
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, escape

Notes

Known escape mutations in B*57 epitopes were studied in a Kenyan cohort of clades A1 and D. The protective effect of B*57 on disease progression was confirmed for clade A1. In some epitopes, HLA B*57-driven evolution differed between clades.
B*57-associated variation from the consensus KAFSPEVIPMF was more common in clade A1 than in clade D. In addition to previously-described variants A163G and A163G/S165N, novel K162X substitutions were also common in clade A1.

References

McKinnon2009 Lyle R. McKinnon, Rupert Capina, Harold Peters, Mark Mendoza, Joshua Kimani, Charles Wachihi, Anthony Kariri, Makobu Kimani, Meika Richmond, Sandy Koesters Kiazyk, Keith R. Fowke, Walter Jaoko, Ma Luo, T Blake Ball, and Francis A. Plummer. Clade-Specific Evolution Mediated by HLA-B*57/5801 in Human Immunodeficiency Virus Type 1 Clade A1 p24. J Virol, 83(23):12636-12642, Dec 2009. PubMed ID: 19759140. Show all entries for this paper.

Displaying record number 57354

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(240-249)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Relative replication capacity assay
Keywords	escape, mutation acquisition, elite controllers

Notes

A dual mechanism for control of HIV replication in elite controllers (EC) is suggested. First, loss of viral fitness is seen more in EC versus viremic subjects associated with unique variations within and flanking immunodominant epitope TW10. Second, strong CTL responses were detected to the above variants.
Virus from 50 subjects including EC and viremics was studied in Gag. The typical T242N mutation in TW10 was not associated with significant differences between both groups.
KF11 epitope was used as a control. Viremic subjects showed stronger responses to KF11 than EC did.

References

Miura2009a Toshiyuki Miura, Mark A. Brockman, Arne Schneidewind, Michael Lobritz, Florencia Pereyra, Almas Rathod, Brian L. Block, Zabrina L. Brumme, Chanson J. Brumme, Brett Baker, Alissa C. Rothchild, Bin Li, Alicja Trocha, Emily Cutrell, Nicole Frahm, Christian Brander, Ildiko Toth, Eric J. Arts, Todd M. Allen, and Bruce D. Walker. HLA-B57/B*5801 Human Immunodeficiency Virus Type 1 Elite Controllers Select for Rare Gag Variants Associated with Reduced Viral Replication Capacity and Strong Cytotoxic T-Lymphocyte Recognition. J Virol, 83(6):2743-2755, Mar 2009. PubMed ID: 19116253. Show all entries for this paper.

Displaying record number 57400

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection, in vitro stimulation or selection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	TCR usage, assay or method development

Notes

By using a modified spectratyping (immunoscoping) method, epitope-specific TCR breadth and sequences were quantitated rapidly. Overall magnitude of HIV-1 specific CTL responses to chronic infection were limited by the clonal breadth of TCR generated against HIV-1 epitopes tested in 12 patients with chronic, untreated infection.
CTL response specific to epitope KF11 was studied, TCR usage was BV19, BV11 and BV18 in patient 00036; BV19, BV06a and BV25 in patient 00052.

References

Balamurugan2010 Arumugam Balamurugan, Hwee L. Ng, and Otto O. Yang. Rapid T Cell Receptor Delineation Reveals Clonal Expansion Limitation of the Magnitude of the HIV-1-Specific CD8+ T Cell Response. J. Immunol., 185(10):5935-5942, 15 Nov 2010. PubMed ID: 20944001. Show all entries for this paper.

Displaying record number 57414

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods
Keywords	acute/early infection

Notes

Escape mutations alone do not account for virological outcome in early-infected, untreated, HLA-B*57+ HIV-1 patients. 5 patients were studied longitudinally up to a maximum of 36 months: 3 presented escape mutations that did not result in increased viremia and 2 patients who presented an increase in VL had not developed new escape or compensatory mutations.
This epitope did not vary in any of the patients under study. Even though Clade C KF11 develop mutations at position A163 that are associated with increased VL, these Clade B viruses did not change at position 163 even in chronic progressors.

References

Durand2010 Christine M. Durand, Karen A. O'Connell, Linda G. Apuzzo, Susan J. Langan, Hejab Imteyaz, Aima A. Ahonkhai, Christina M. Ceccato, Thomas M. Williams, Joseph B. Margolick, and Joel N. Blankson. HIV-1 Gag Evolution in Recently Infected Human Leukocyte Antigen-B*57 Patients with Low-Level Viremia. AIDS, 24(15):2405-2408, 24 Sep 2010. PubMed ID: 20671542. Show all entries for this paper.

Displaying record number 57416

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Degranulation, CD107a and b cell surface mobilization, Intracellular cytokine staining
Keywords	elite controllers

Notes

Viremic control among HLA-B*57 controllers was identified as being due to the lack of fitness-restoring viral capsid compensatory mutations (in response to escapes) and not superior T-cell responses.
11 >10-year child and adolescent survivors of perinatal HIV infection including 4 controllers showed that breadth and magnitude of CTL response is higher among progressors. Exclusive targeting of epitopes from Gag, RT was seen in controllers, but progressors also mounted response to Nef and other proteins' epitopes. There was no individual, specially targeted epitope in controllers.
Cytokine production by CTL is not superior in long-term surviving controllers, but correlates with the specific epitope that stimulates its release.
Patient CH-11, a progressor on HAART exhibited a highly polyfunctional response to this immunodominant epitope, KF11, producing IFN-gamma and TNF-alpha, but hardly any degranulation or cytokine production was seen in the same assay against another Gag epitope, QW9, QASQEVKNW.
KF11 rarely escapes in Clade B infection and mutations were observed only in 2 controllers and no progressors studied.

References

Tang2010 Yanhua Tang, Sihong Huang, Jacqueline Dunkley-Thompson, Julianne C. Steel-Duncan, Elizabeth G. Ryland, M. Anne St. John, Rohan Hazra, Celia D. C. Christie, and Margaret E. Feeney. Correlates of Spontaneous Viral Control among Long-Term Survivors of Perinatal HIV-1 Infection Expressing Human Leukocyte Antigen-B57. AIDS, 24(10):1425-1435, 19 Jun 2010. PubMed ID: 20539088. Show all entries for this paper.

Displaying record number 58815

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Tetramer binding
Keywords	elite controllers

Notes

The role of central memory T cells was investigated in elite control of HIV-1 infection in subjects. Highly functional, broadly directed memory T cells populations were found in elite controllers (EC) that are capable of suppressing HIV-1 in vitro and thus containing VL and infection.
When EC were compared to chronic progressors (CP) and ART-treated subjects, expansion of Gag-specific responses was significantly higher for EC and it was of mainly new, previously unrecognized CTL responses. Epitope-specific CTL responses that were previously not detectable can be expanded ex vivo and they are polyfunctional, inhibiting of viral replication, and contain memory cells that have strong proliferative capacity.
B*57-restricted KF11-specific CTL were capable of expanding ex vivo from 0.02 to 10% of the culture, and most of these were memory T cells.

References

Ndhlovu2012 Zaza M. Ndhlovu, Jacqueline Proudfoot, Kevin Cesa, Donna Marie Alvino, Ashley McMullen, Seanna Vine, Eleni Stampouloglou, Alicja Piechocka-Trocha, Bruce D. Walker, and Florencia Pereyra. Elite Controllers with Low to Absent Effector CD8+ T Cell Responses Maintain Highly Functional, Broadly Directed Central Memory Responses. J. Virol., 86(12):6959-3969, Jun 2012. PubMed ID: 22514340. Show all entries for this paper.

Displaying record number 60640

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF-11
Subtype	B, C
Species (MHC/HLA)	human(B57, B5701, B5703, B58, B5801, B63)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Subtype-specific substitutions in two HIV Gag regions (fragments F1, amino acids (aa) 5-46, and F2 aa 100-143) result in novel adaptations that affect epitope processing efficiency. Consequent low epitope abundance is associated with weak T cell response and greater immune escape and therefore with disease state. Conversely, epitopes from these regions when restricted by certain rare HLA I alleles, are associated with greater production and resulting CTL response, therefore delayed disease progression.
Most epitopes were found to be processed as precursors with N-terminal extensions beyond the optimal epitope. Only 4 epitopes in this region were associated with delayed progression - HLA-B*5701/03-restricted IW9 (ISPRTLNAW), KF11 (KAFSPEVIPMF), TW10 (TSTLQEQIGW) and HLA-B*2705-restricted KK10 (KRWIILGLNK).
Regardless of ethnic group, white or African, a significant three-way interaction was found between HLA allelic frequency, epitope yield and ethnicity for epitopes of N-terminal fragment F1 (NF1) and C-terminal as well as middle F2 (CF2 and MF2). C-terminal F1 (CF1) epitope yields however, showed a significant difference between ethnic groups. Also, for identical HLA-mediated selection pressure in both Africans and whites, HIV-C had a lower concentration than HIV-B, especially at lower HLA allelic frequencies.
Epitope KAFSPEVIPMF, KF-11, is from fragment F1, and restricted by HLA-B*57, B*5701,B*5703, B*58, B*5801, B*63. No WAWVKVIEEKAFSPEVIPMF, KF-11's subtype B, natural processed epitope form, accumulated after 4 hours processing by constitutive or immuno-proteasomes. For subtype C, the natural processed form was WAWVKVIEEKAFSPEVIPMF, 6% 4h post-constitutive- and 3% post-immuno-proteasomal processing.

References

Tenzer2014 Stefan Tenzer, Hayley Crawford, Phillip Pymm, Robert Gifford, Vattipally B. Sreenu, Mirjana Weimershaus, Tulio de Oliveira, Anne Burgevin, Jan Gerstoft, Nadja Akkad, Daniel Lunn, Lars Fugger, John Bell, Hansjörg Schild, Peter van Endert, and Astrid K. N. Iversen. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification. Cell Rep., 7(2):448-463, 24 Apr 2014. PubMed ID: 24726370. Show all entries for this paper.

Displaying record number 57592

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	(B57, B58)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

Responses to specific B57/58, B27, and B35-restricted epitopes were tested in a cohort of 45 subjects during primary infection. The presence of certain B57/58, B27, and B35-restricted T-cell responses during primary infection better defined disease progression than the HLA genotype alone, suggesting that it is the HIV-specific CD8+ T-cells and not the presence of a particular HLA allele, that determine disease progression.
6/9 B57/58-positive subjects responded to KAFSPEVIPMF, and 34% of the patients' total response magnitude was derived from this specific response.
This epitope was 84% conserved among M-group sequences and 97% conserved among B-subtype sequences.
Epitope-specific HLA-B responses to TW10 and KF11 delayed declines in CD4+ T-cell counts more than 8 years in HLA-B57/58-positive subjects.
The presence of responses to KF11 delayed declines in CD4+ T-cell counts to 3.5 to 8.2 times longer or more than 8 years in HLA-B57/58-positive subjects.

References

Dinges2010 Warren L. Dinges, Julia Richardt, David Friedrich, Emilie Jalbert, Yi Liu, Claire E. Stevens, Janine Maenza, Ann C. Collier, Daniel E. Geraghty, Jeremy Smith, Zoe Moodie, James I. Mullins, M. Juliana McElrath, and Helen Horton. Virus-Specific CD8+ T-Cell Responses Better Define HIV Disease Progression than HLA Genotype. J. Virol., 84(9):4461-4468, May 2010. PubMed ID: 20147397. Show all entries for this paper.

Displaying record number 57776

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B57, B5801)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Relative replication capacity assay
Keywords	responses in children, rate of progression

Notes

Immunological responses in progressing and slow-progressing C-clade infected infants suggest a link between slow progression and HLA-B*57/5801 epitope-specific Gag mutations of the transmitted virus and not due to coreceptor usage or the presence of Nef deletions/insertions.
All viral isolates studied contained polymorphisms in at least one of the 4 Gag epitopes studied (ISW9, KF11, TW10, QW9).
In a viral replication assay, T cells were infected with wild-type and variants of the 4 Gag epitopes studied (ISW9, KF11, TW10, QW9) and the CypA binding loop. Viruses from progressing infants showed higher replicative capacity than viruses from slow-progressing infants. Thus B*57/5801-related mutations in p24 epitopes may contributed to low replicative capacity.
In 6/8 subjects, the early viral isolates contained variations in TW10 positions 3 and 7 (T3S, T3N, I7V, I7L) that have previously been shown to reduce replicative capacity. In 2/3 progressing infants, mutations in TW10 were accompanied by upstream compensatory changes at H219Q, I223P, and M228I/L.

References

Prado2010 Julia G. Prado, Andrew Prendergast, Christina Thobakgale, Claudia Molina, Gareth Tudor-Williams, Thumbi Ndung'u, Bruce D. Walker, and Philip Goulder. Replicative Capacity of Human Immunodeficiency Virus Type 1 Transmitted from Mother to Child Is Associated with Pediatric Disease Progression Rate. J. Virol., 84(1):492-502, Jan 2010. PubMed ID: 19828603. Show all entries for this paper.

Displaying record number 57685

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B57, B5801)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	immunodominance, characterizing CD8+ T cells

Notes

The antiviral effectiveness of HLA-B*57/58 and HLA-Cw*07 restricted CD8+ T-cell responses did not differ significantly in polyfunctionality, suggesting that the loss of polyfunctionality during disease progression is independent of the restricting HLA allele. There were no differences in the polyfunctionality of T cells specific to wild type versus mutated epitopes, suggesting that sequence variation does not significantly impact CD8 T-cell polyfunctionality in chronic infection.
1/9 HLA-B*57/58- and HLA-Cw*07-positive subjects had a positive Elispot response to this epitope. Among 37 HLA-B*57/58- and HLA-Cw*07-positive subjects, this epitope was predominantly presented by HLA-B*5703.

References

Mkhwanazi2010 Nompumelelo Mkhwanazi, Christina F. Thobakgale, Mary van der Stok, Shabashini Reddy, Zenele Mncube, Fundisiwe Chonco, Bruce D. Walker, Marcus Altfeld, Philip J. R. Goulder, and Thumbi Ndung'u. Immunodominant HIV-1-Specific HLA-B- and HLA-C-Restricted CD8+ T Cells Do Not Differ in Polyfunctionality. Virology, 405(2):483-491, 30 Sep 2010. PubMed ID: 20638093. Show all entries for this paper.

Displaying record number 55670

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B57, B5801)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords

Notes

Transmission of HIV-1-escape variants from individuals with protective HLA-B*57/-B*5801 alleles to those without these alleles was studied to determine if infection with such replication-deficient mutants offered any advantage to the new host. Dependency between slower rate of disease progression in the newly infected subject and protective genotype of the infecting individual was suggested.
Epitope KF11, KAFSPEVIPMF, was found with the A163X mutation in 3 sequences. Other variations found in KF11 were (E)KAFSPEVIPMF(i), (E)KgFSPEVIPMF(T) and (E)KsFSPEVIPMF(T).

References

Chopera2008 Denis R. Chopera, Zenda Woodman, Koleka Mlisana, Mandla Mlotshwa, Darren P. Martin, Cathal Seoighe, Florette Treurnicht, Debra Assis de Rosa, Winston Hide, Salim Abdool Karim, Clive M. Gray, Carolyn Williamson, and CAPRISA 002 Study Team. Transmission of HIV-1 CTL Escape Variants Provides HLA-Mismatched Recipients with a Survival Advantage. PLoS Pathog, 4(3):e1000033, Mar 2008. PubMed ID: 18369479. Show all entries for this paper.

Displaying record number 57191

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(329-343)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57, B5801)
Immunogen	HIV-1 infection
Patient MHC/HLA	B27, B57; B27, B5801; B57; B57; B57
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, autologous responses, elite controllers

Notes

A longitudinal study of 6 elite controllers (ES) over 5 years examined proviral versus plasma Gag sequences for mutation, and compared it to CTL response of the autologous variants. ES were found to control viremia despite plasma viral replication and epitope evolution.
Late plasma clones from subject ES7 had the S173T mutation immediately adjacent to KF11 epitope, from KAFSPEVIPMF|S to KAFSPEVIPMF|t. Subjects ES9 and ES31 showed mutation in one position in proviral and plasma clones - KsFSPEVIPMF.

References

OConnell2010 Karen A. O'Connell, Timothy P. Brennan, Justin R. Bailey, Stuart C. Ray, Robert F. Siliciano, and Joel N. Blankson. Control of HIV-1 in Elite Suppressors Despite Ongoing Replication and Evolution in Plasma Virus. J. Virol., 84(14):7018-7028, Jul 2010. PubMed ID: 20444904. Show all entries for this paper.

Displaying record number 55047

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	binding affinity, immunodominance, optimal epitope

Notes

CTL responses were tested for both HIV-1 and EBV derived epitopes restricted by HLA-A, -B and -C alleles. HLA-B alleles more frequently induce detectable responses and that the responses are generally of greater magnitude than those for HLA-A and -C alleles.
The magnitude and frequency of CTL recognition were related to each other and that TCR avidity for HLA/peptide complexes is a more important determinant for magnitude of response than peptide binding affinity to HLA.
EBV response patterns were not significantly altered by HIV coinfection.
Epitope KAFSPEVIPMF elicited a magnitude of response of 740 SFC with a functional avidity of 0.005nM and binding affinity of 21.

References

Bihl2006 Florian Bihl, Nicole Frahm, Loriana Di Giammarino, John Sidney, Mina John, Karina Yusim, Tonia Woodberry, Kaori Sango, Hannah S. Hewitt, Leah Henry, Caitlyn H. Linde, John V. Chisholm, III, Tauheed M. Zaman, Eunice Pae, Simon Mallal, Bruce D Walker, Alessandro Sette, Bette T. Korber, David Heckerman, and Christian Brander. Impact of HLA-B Alleles, Epitope Binding Affinity, Functional Avidity, and Viral Coinfection on the Immunodominance of Virus-Specific CTL Responses. J. Immunol., 176(7):4094-4101, 1 Apr 2006. PubMed ID: 16547245. Show all entries for this paper.

Displaying record number 164

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords	immunodominance

Notes

Only 4/11 HLA-A2+ HIV+ individuals had CTL that reacted to SLYNTVATL, calling into question whether it is immunodominant.
95 optimally-defined peptides from this database were used to screen for INFγ responses to other epitopes.
1/11 of the A2+ individuals was HLA A*0201, A1, B57 and responded to four B57 epitopes and two others.

References

Betts2000 M. R. Betts, J. P. Casazza, B. A. Patterson, S. Waldrop, W. Trigona, T.-M Fu, F. Kern, L. J. Picker, and R. A. Koup. Putative Immunodominant Human Imunodeficiency Virus-Specific CD8+ T Cell Responses Cannot Be Predicted by Major Histocompatibility Complex Class I Haplotype. J. Virol., 74:9144-9151, 2000. PubMed ID: 10982361. Show all entries for this paper.

Displaying record number 1175

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24( SF2)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons, immunodominance

Notes

The CTL-dominant response was focused on this epitope in a HIV+ Caucasian living in Boston -- this epitope is not among the most recognized peptides in the study.
Three peptides GSEELRSLYNTVATL (p17 residues 71-85), SALSEGATPQDLNTMLNTVG (p24 41-60), and WEKIRLRPGGKKKYKLK (p17 16-30) contained the dominant Gag-specific epitope in 31/44 B-clade infected individuals from Boston who showed Gag-CTL responses.
Five peptides RLRPGGKKHYMIKHLVW (p17 20-36), ELRSLYNTVATLYCV (p17Gag 74-88), SALSEGATPQDLNTMLNTVG (p24 41-60), FRDYVDRFFKTLRAEQA (p24 161-177), and SILDIKQGKEPFRDY (p24 149-164) contained dominant Gag-specific epitopes in 32/37 C-clade infected subjects from South Africa.

References

Goulder2000 P. J. Goulder, C. Brander, K. Annamalai, N. Mngqundaniso, U. Govender, Y. Tang, S. He, K. E. Hartman, C. A. O'Callaghan, G. S. Ogg, M. A. Altfeld, E. S. Rosenberg, H. Cao, S. A. Kalams, M. Hammond, M. Bunce, S. I. Pelton, S. A. Burchett, K. McIntosh, H. M. Coovadia, and B. D. Walker. Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and caucasoid adults and children. J. Virol., 74:5679-90, 2000. PubMed ID: 10823876. Show all entries for this paper.

Displaying record number 1297

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag( SF2)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Three CTL responses in patient PI004, to epitopes TSTLQEQIGW, ISPRTLNAW, and KAFSPEVIPMF, were evident early after infection; CTL responses to SLYNTVATL, QASQEVKNW, EIYKRWII, and FLKEKGGL were detectable at 5 months post-infection and beyond.

References

Goulder2001 P. J. Goulder, M. M. Addo, M. A. Altfeld, E. S. Rosenberg, Y. Tang, U. Govender, N. Mngqundaniso, K. Annamalai, T. U. Vogel, M. Hammond, M. Bunce, H. M. Coovadia, and B. D. Walker. Rapid Definition of Five Novel HLA-A*3002-Restricted Human Immunodeficiency Virus-Specific Cytotoxic T-Lymphocyte Epitopes by Elispot and Intracellular Cytokine Staining Assays. J. Virol., 75(3):1339-1347, Feb 2001. URL: http://jvi.asm.org/cgi/content/full/75/3/1339. PubMed ID: 11152507. Show all entries for this paper.

Displaying record number 1380

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KAF
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, acute/early infection

Notes

Patients who started therapy at acute HIV-1 infection (three with sustained therapy, two with limited therapy upon early infection) had strong HIV specific CD4 proliferative responses and were able to maintain a CTL response even with undetectable viral load -- three patients that had delayed initiation of HAART had no HIV specific CD4 proliferative responses and lost their CTL responses when HAART was eventually given and their viral loads became undetectable.
None of the 8 study subjects recognized this epitope but none were HLA B57+.

References

Oxenius2000b A. Oxenius, D. A. Price, P. J. Easterbrook, C. A. O'Callaghan, A. D. Kelleher, J. A. Whelan, G. Sontag, A. K. Sewell, and R. E. Phillips. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc. Natl. Acad. Sci. U.S.A., 97(7):3382-7, 28 Mar 2000. URL: http://www.pnas.org/cgi/content/full/97/7/3382. PubMed ID: 10737796. Show all entries for this paper.

Displaying record number 1411

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

HLA tetramers to six epitopes were used to study HLA-A2, B8 and B57 CTL in 54 patients -- HIV-specific tetramer positive cells were inversely correlated with viral load in patients with high CD4, but in patients with CD4 T-cells below 400 high tetramer frequencies were found despite high viral load.
Most patients have high levels of HIV-specific T-cell expansions, but many of these cells aren't functional.
In 15 of the patients, the proportion of IFN gamma producing tetramer cells correlated with AIDS-free survival.

References

Kostense2001 S. Kostense, G. S. Ogg, E. H. Manting, G. Gillespie, J. Joling, K. Vandenberghe, E. Z. Veenhof, D. van Baarle, S. Jurriaans, M. R. Klein, and F. Miedema. High viral burden in the presence of major HIV-specific CD8(+) T cell expansions: evidence for impaired CTL effector function. Eur. J. Immunol., 31(3):677-86, Mar 2001. PubMed ID: 11241270. Show all entries for this paper.

Displaying record number 1555

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172 SF2)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, acute/early infection

Notes

Therapy provided during acute infection resulted in a narrower CTL response, stronger T help response, and a less diverse viral population than was seen in individuals treated during chronic infection.
The breadth and specificity of the response was determined using ELISPOT by studying 19 individuals with pre-seroconversion therapy (Group 1), 11 individuals with primary infection but post-seroconversion therapy (Group 2), and 10 individuals who responded to HAART given during chronic infection (Group 3), using 259 overlapping peptides spanning p17, p24, RT, gp41, gp120 and Nef.
Previously described and newly defined optimal epitopes were tested for CTL response.
Number of HLA-B57+ individuals that had a CTL response to this epitope broken down by group: 0/0 group 1, 0/0 group 2, and 2/2 group 3.

References

Altfeld2001b M. Altfeld, E. S. Rosenberg, R. Shankarappa, J. S. Mukherjee, F. M. Hecht, R. L. Eldridge, M. M. Addo, S. H. Poon, M. N. Phillips, G. K. Robbins, P. E. Sax, S. Boswell, J. O. Kahn, C. Brander, P. J. Goulder, J. A. Levy, J. I. Mullins, and B. D. Walker. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med., 193(2):169-80, 15 Jan 2001. URL: http://www.jem.org/cgi/content/full/193/2/169. PubMed ID: 11148221. Show all entries for this paper.

Displaying record number 1708

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(163-174)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Combined tetramer and intracellular cytokine staining was used to study the function of circulating CD8+ T cells specific for HIV and CMV.
HIV-specific CD8+ T cells expressed lower levels of perforin than CMV-specific CD8+ T cells from the same donor, and this was associated with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation.
In most donors, between 50% and 95% of the activated virus-specific CD8+ T cells produced IFN-γ and MIP-1β with a distinct subset that failed to produce TNF-α.

References

Appay2000 V. Appay, D. F. Nixon, S. M. Donahoe, G. M. Gillespie, T. Dong, A. King, G. S. Ogg, H. M. Spiegel, C. Conlon, C. A. Spina, D. V. Havlir, D. D. Richman, A. Waters, P. Easterbrook, A. J. McMichael, and S. L. Rowland-Jones. HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J. Exp. Med., 192(1):63-75, 3 Jul 2000. URL: http://www.jem.org/cgi/content/full/192/1/63. PubMed ID: 10880527. Show all entries for this paper.

Displaying record number 52325

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KAF
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

Using previously defined epitopes Oxenius2000b,Oxenius2001b in an IFN? Elispot assay, 13 chronically HIV-1 infected patients were studied over a period including therapy with standard treatment interruptions (STI).
STIs induced increased recognition of CTL epitopes, but there was no correlation between CTL responses with viral rebound rates, plateau viral loads, or clearance rates.

References

Oxenius2002b Annette Oxenius, Angela R. McLean, Marek Fischer, David A. Price, Sarah J. Dawson, Roland Hafner, Christine Schneider, Helen Joller, Bernard Hirschel, Rodney E. Phillips, Rainer Weber, Huldrych F. Günthard, and Swiss HIV Cohort Study Group. Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Do Not Predict Viral Growth and Clearance Rates During Structured Intermittent Antiretroviral Therapy. J. Virol., 76(20):10169-10176, Oct 2002. PubMed ID: 12239291. Show all entries for this paper.

Displaying record number 52622

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	A*0201, A3, B44, B57, Cw5, Cw6
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection, early-expressed proteins

Notes

All proteins were scanned and optimal epitopes were mapped in a study of CD8+ gamma IFN T-cell responses in 21 men within 15-92 days post-HIV-1 infection. Subjects initially showed narrow immune responses with a mean of 2.3 epitopes recognized per patient. The immune response broadened later in infection. No correlation between the plasma viral load and the number of recognized epitopes or the frequency of IFN-gamma secreting cells was observed, and there was no correlation between the functional avidity of responses and the abundance of IFN-secreting cells that recognized the epitope. The first epitopes to be recognized did not tend to be the most avid, and earliest responses tended to be directed against Nef, Tat, Vpr, and Env.
All HIV-1 proteins except Vpu were recognized, and responses to a total of 41 optimal epitopes were characterized; 24 had been identified previously. 48% of the total T-cell responses were directed against Nef and 43% were directed against Gag.
Alleles A3, B35, B57, and B62 were more frequently recognized than alleles A1, A2, A30, and A44 e.g., during primary infection. 2/10 patients, 1372 and 1397, recognized A2-restricted epitopes. The common A2-restricted epitopes Gag SL9 and Pol IV9 were not recognized in peptide tetramer-binding assays.

References

Cao2003 Jianhong Cao, John McNevin, Sarah Holte, Lisa Fink, Lawrence Corey, and M. Juliana McElrath. Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+ T Cells in Primary HIV-1 Infection. J. Virol., 77(12):6867-6878, Jun 2003. PubMed ID: 12768006. Show all entries for this paper.

Displaying record number 52728

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods	Intracellular cytokine staining
Keywords	immunodominance, genital and mucosal immunity

Notes

Predefined immunodominant peptide responses were used to compare CD8+ T-cell responses in the blood and cervix of 16 HIV+ Kenyan sex workers. Cervical responses were detected in 8/10 women from whom adequate samples could be obtained. The frequency of the CD8+ T-cell response in the genital tract was comparable to the blood, with a trend toward being slightly higher.
The immunodominant response was to this epitope in the PBMC of 10/16 patients (Kaul et al. 2001, AIDS, 107:1303).

References

Kaul2003 Rupert Kaul, Paul Thottingal, Joshua Kimani, Peter Kiama, Charles W. Waigwa, Job J. Bwayo, Francis A. Plummer, and Sarah L. Rowland-Jones. Quantitative Ex Vivo Analysis of Functional Virus-Specific CD8 T Lymphocytes in the Blood and Genital Tract of HIV-Infected Women. AIDS, 17(8):1139-1144, May 2003. PubMed ID: 12819514. Show all entries for this paper.

Displaying record number 52844

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(163-174)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	A0201, A3, B57, Cw06, Cw07; A01, A0201, B08, B*57, Cw6, Cw7
Country	United States
Experimental methods	Cytokine production, Degranulation, CD107a and b cell surface mobilization, Intracellular cytokine staining, Tetramer binding
Keywords	TCR usage

Notes

Both cytokine production and degranulation in HIV-1 specific and CMV specific CD8+ T -cells occurs at high peptide concentrations together with TCR downregulation. Only degranulation is observed at lower peptide concentrations with no observed TCR downregulation. Thus the nature of CTL response depends not on the specific T cell clonotype or antigen, but on the concentration of Ag presented on APCs.

References

Betts2004 Michael R. Betts, David A. Price, Jason M. Brenchley, Karin Loré, F. Javier Guenaga, Anna Smed-Sorensen, David R. Ambrozak, Stephen A. Migueles, Mark Connors, Mario Roederer, Daniel C. Douek, and Richard A. Koup. The Functional Profile of Primary Human Antiviral CD8+ T Cell Effector Activity Is Dictated by Cognate Peptide Concentration. J. Immunol., 172(10):6407-6417, 15 May 2004. PubMed ID: 15128832. Show all entries for this paper.

Displaying record number 52920

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	epitope processing, escape

Notes

This study characterizes the N-terminal flanking position of the epitope ISPRTLNAW, and mutations in this position are thought to impact processing. The B57 epitope KAFSPEVIPMF was used as a positive control in this study.

References

Draenert2004a Rika Draenert, Sylvie Le Gall, Katja J. Pfafferott, Alasdair J. Leslie, Polan Chetty, Christian Brander, Edward C. Holmes, Shih-Chung Chang, Margaret E. Feeney, Marylyn M. Addo, Lidia Ruiz, Danni Ramduth, Prakash Jeena, Marcus Altfeld, Stephanie Thomas, Yanhua Tang, Cori L. Verrill, Catherine Dixon, Julia G. Prado, Photini Kiepiela, Javier Martinez-Picado, Bruce D. Walker, and Philip J. R. Goulder. Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection. J. Exp. Med., 199(7):905-915, 5 Apr 2004. PubMed ID: 15067030. Show all entries for this paper.

Displaying record number 52924

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(155-172 B con)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	variant cross-reactivity

Notes

CD8+ T-cell responses that persisted in individuals with advanced disease were studied; most of the optimal epitopes defined were recognized with intermediate to high avidity. On average 13 (range, 2-39) epitopic regions were targeted in an average of 6 proteins (range, 1-8). HAART resulted in decrease in antigen and reduction in gamma IFN EliSpot responses, suggesting active responses to autologous virus. The lack of mutations within most viral epitopes suggest that persistent CTL through late disease do not exert strong immune selection pressure, yet the Elispot assays show robust responses, suggesting to the authors that gamma IFN-based screening methods may not reveal functional CD8+ T-cell impairment in patients with AIDS.
2 subjects recognized this epitope, 1 with high functional avidity, 1 with intermediate. Autologous sequence revealed no substitutions in this epitope compared to the B consensus.

References

Draenert2004b R. Draenert, C. L. Verrill, Y. Tang, T. M. Allen, A. G. Wurcel, M. Boczanowski, A. Lechner, A. Y. Kim, T. Suscovich, N. V. Brown, M. M. Addo, and B. D. Walker. Persistent Recognition of Autologous Virus by High-Avidity CD8 T Cells in Chronic, Progressive Human Immunodeficiency Virus Type 1 Infection. J. Virol., 78(2):630-641, Jan 2004. PubMed ID: 14694094. Show all entries for this paper.

Displaying record number 53045

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

A high-risk seronegative group of 29 homosexual men showed reduced cellular in vitro susceptibility for HIV infection and enhanced production of RANTES compared to 15 men who went on to seroconvert. Significantly higher frequencies of HLA A*11, A*31 and Cw*15 were also found in the high risk seronegative men. Both groups of men had low frequencies of HIV-1 specific CD8+ T-cells, which may signify exposure more than protection from infection.
1/2 HLA B57+ infection-resistant men, compared to 0/1 pre-seroconversion men who went on to become infected, reacted to this epitope.

References

Koning2004 Fransje A. Koning, Christine A. Jansen, Jos Dekker, Richard A. Kaslow, Nicole Dukers, Debbie van Baarle, Maria Prins, and Hanneke Schuitemaker. Correlates of Resistance to HIV-1 Infection in Homosexual Men with High-Risk Sexual Behaviour. AIDS, 18(8):1117-1126, 21 May 2004. PubMed ID: 15166527. Show all entries for this paper.

Displaying record number 53205

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	(162-172 B consensus)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	immunodominance, characterizing CD8+ T cells

Notes

This study characterizes an escape mutation in a C-terminal flanking residue of the HLA-A3 gag p17 KK9 epitope that inhibits processing, and is embedded in the overlapping HLA-A3 RK9 epitope.
The immune response was tracked in subject AC-38. The acute immunodominant response was to the B57 TW10 epitope; this response declined following viral escape (tsNlqeqigw) by day 64. The p17 KK9 and RK9 became immunodominant, but then declined as the escape mutation arose. FK11 is 1 of 3 other strong responses that persisted, along with 1 sub-dominant response.

References

Allen2004 Todd M Allen, Marcus Altfeld, Xu G. Yu, Kristin M. O'Sullivan, Mathias Lichterfeld, Sylvie Le Gall, Mina John, Bianca R. Mothe, Paul K. Lee, Elizabeth T. Kalife, Daniel E. Cohen, Kenneth A. Freedberg, Daryld A. Strick, Mary N. Johnston, Alessandro Sette, Eric S. Rosenberg, Simon A. Mallal, Philip J. R. Goulder, Christian Brander, and Bruce D. Walker. Selection, Transmission, and Reversion of an Antigen-Processing Cytotoxic T-Lymphocyte Escape Mutation in Human Immunodeficiency Virus Type 1 Infection. J. Virol., 78(13):7069-7078, Jul 2004. PubMed ID: 15194783. Show all entries for this paper.

Displaying record number 53308

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	characterizing CD8+ T cells

Notes

HLA class I restricted CD8+ T-cell responses against HIV-1 were analyzed in African patients. Significantly more responses were shown to be HLA-B restricted. Viral load, CD4 count, and thus rate of disease progression were also associated with HLA-B alleles. In addition, the selection pressure imposed on HIV-1 by HLA-B alleles was shown to be substantially greater than by other alleles.
This epitope was suggested to be the epitope within a longer reactive peptide based on correspondence with a known epitope in the HIV database. Also, a significantly higher frequency of people in the Durban cohort who reacted with the peptide had this HLA type.

References

Kiepiela2004 Photini Kiepiela, Alasdair J. Leslie, Isobella Honeyborne, Danni Ramduth, Christina Thobakgale, Senica Chetty, Prinisha Rathnavalu, Corey Moore, Katja J. Pfafferott, Louise Hilton, Peter Zimbwa, Sarah Moore, Todd Allen, Christian Brander, Marylyn M. Addo, Marcus Altfeld, Ian James, Simon Mallal, Michael Bunce, Linda D. Barber, James Szinger, Cheryl Day, Paul Klenerman, James Mullins, Bette Korber, Hoosen M. Coovadia, Bruce D. Walker, and Philip J. R. Goulder. Dominant Influence of HLA-B in Mediating the Potential Co-Evolution of HIV and HLA. Nature, 432(7018):769-775, 9 Dec 2004. LA-UR 04-5920. PubMed ID: 15592417. Show all entries for this paper.

Displaying record number 53406

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	Intracellular cytokine staining, T-cell Elispot, Tetramer binding
Keywords	rate of progression, acute/early infection, characterizing CD8+ T cells

Notes

Acute HIV-1 infection induces massive activation of HIV-specific and non-HIV-specific CD8+ T-cells resulting in differentiation of these cells. High differentiation of CD8+ T-cells is correlated with disease progression. Differentiation is a natural process but it can be driven by elevated immune activation, such as in HIV infection.

References

Papagno2004 Laura Papagno, Celsa A. Spina, Arnaud Marchant, Mariolina Salio, Nathalie Rufer, Susan Little, Tao Dong, Gillian Chesney, Anele Waters, Philippa Easterbrook, P. Rod Dunbar, Dawn Shepherd, Vincenzo Cerundolo, Vincent Emery, Paul Griffiths, Christopher Conlon, Andrew J. McMichael, Douglas D. Richman, Sarah L. Rowland-Jones, and Victor Appay. Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 Infection. PLoS Biol., 2(2):E20, Feb 2004. PubMed ID: 14966528. Show all entries for this paper.

Displaying record number 53493

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, escape, characterizing CD8+ T cells, viral fitness and reversion

Notes

Two-thirds of all mutations arising in non-envelope proteins during the transition from acute to chronic infection were found to be due to either CD8 T-cell-associated selective pressures or reversion of HLA-I-associated mutations selected in a previous host.The predominance of escape mutations at highly polymorphic sites was observed across different HIV-1 clades.
This epitope was quite conserved in people carrying B57, but two substitutions were found in 11 B57+ individuals tested: kNfspevipmf and kafspeIipmf.

References

Allen2005a Todd M. Allen, Marcus Altfeld, Shaun C. Geer, Elizabeth T. Kalife, Corey Moore, Kristin M. O'Sullivan, Ivna DeSouza, Margaret E. Feeney, Robert L. Eldridge, Erica L. Maier, Daniel E. Kaufmann, Matthew P. Lahaie, Laura Reyor, Giancarlo Tanzi, Mary N. Johnston, Christian Brander, Rika Draenert, Jurgen K. Rockstroh, Heiko Jessen, Eric S. Rosenberg, Simon A. Mallal, and Bruce D. Walker. Selective Escape from CD8+ T-Cell Responses Represents a Major Driving Force of Human Immunodeficiency Virus Type 1 (HIV-1) Sequence Diversity and Reveals Constraints on HIV-1 Evolution. J. Virol., 79(21):13239-13249, Nov 2005. PubMed ID: 16227247. Show all entries for this paper.

Displaying record number 53549

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A3, B57, B7, Cw6, Cw7
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords

Notes

Two-thirds of all mutations arising in non-envelope proteins during the transition from acute to chronic infection were found to be due to either CD8 T-cell-associated selective pressures or reversion of HLA-I-associated mutations selected in a previous host.The predominance of escape mutations at highly polymorphic sites was observed across different HIV-1 clades.
This epitope was reactive, but escape mutations did not accrue in it over time.

References

Displaying record number 159

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Two strong clonal CTL responses were generated in donor 026-BMC (HLA A3/-, B42/B57, Cw7/17) against different optimal versions of this epitope, one 8 amino acids long, one 11.
Improved stabilization of the B57-peptide complex was demonstrated by the 11mer which fits the B57 binding motif, relative to the 8 mer, which does not.
B57 tolerates marked difference in optimal peptide length -- and B57 is associated with non-progressive infection.

References

Goulder2000a P. J. Goulder, Y. Tang, S. I. Pelton, and B. D. Walker. HLA-B57-Restricted Cytotoxic T-Lymphocyte Activity in a Single Infected Subject toward Two Optimal Epitopes, One of Which Is Entirely Contained Within the Other. J. Virol., 74:5291-5299, 2000. PubMed ID: 10799606. Show all entries for this paper.

Displaying record number 53733

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172 BRU)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B, CRF02_AG
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Cote D'Ivoire
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons

Notes

CD8+ T-cells from HIV-1 CRF02_AG-infected Ivorians could recognize clade B epitopes. No difference was observed in the number of recognized peptide pools between nine French subtype B infected study subjects, and nine CRF02_AG infected Ivorian subjects.
This epitope was recognized by 1/9 CRF02_AG-infected Ivorians, and 1/9 B-infected French subjects.

References

Inwoley2005 André Inwoley, Patricia Recordon-Pinson, Marion Dupuis, Jessintha Gaston, Mathieu Genête, Albert Minga, Franck Letourneur, François Rouet, Jeannine Choppin, Hervé Fleury, Jean-Gérard Guillet, Muriel Andrieu, and ANRS 1220 PRIMO-CI Study Group. Cross-Clade Conservation of HIV Type 1 Nef Immunodominant Regions Recognized by CD8+ T Cells of HIV Type 1 CRF02\_AG-Infected Ivorian (West Africa). AIDS Res. Hum. Retroviruses, 21(7):620-628, Jul 2005. PubMed ID: 16060833. Show all entries for this paper.

Displaying record number 53741

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KAF
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	binding affinity, rate of progression, escape, characterizing CD8+ T cells

Notes

HLA-B57 has been associated with long term non-progression in HIV+ people. The number and responsiveness of CD8 T-cells directed to different Gag peptides presented by HLA-A2, -B8 and B57 were compared. T cells specific for the HLA-B57 epitope KAFSPEVIPMF responded to a higher extent and more readily to antigenic stimulation than those specific for the A2 epitope SLYNTVATL and the B8 epitope EIYKRWII.
Tetramer decay experiments indicate that the HLA-B57 peptide has a higher half-life than the A2 and B8 peptides. The authors point out that CD8+ T cells with high binding affinity may require less help.
Variant forms of the HLA-B57 epitope KAFSPEVIPMF were found in the 3/5 HLA B57+ individuals sequenced, but the variants were always a minor form.

References

Jansen2005a Christine A. Jansen, Stefan Kostense, Kristin Vandenberghe, Nening M. Nanlohy, Iris M. De Cuyper, Erwan Piriou, Erik H. Manting, Frank Miedema, and Debbie van Baarle. High Responsiveness of HLA-B57-Restricted Gag-Specific CD8+ T Cells In Vitro May Contribute to the Protective Effect of HLA-B57 in HIV-Infection. Eur. J. Immunol., 35(1):150-158, Jan 2005. PubMed ID: 15593302. Show all entries for this paper.

Displaying record number 54394

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	B57-KF11(p24)
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, early-expressed proteins

Notes

Immunodominant HIV epitopes in early, primary infection of CTLs were identified and the relative contribution of immune responses restricted to individual HLA class I molecules were studied.
The most frequently recognised epitopes also elicited the greatest CTL response.
HIV-1 Epitope sequence variability was not correlated with immunodominant versus immune sub-dominant responses.
HLA-B*57 and HLA-B*27 restricted responses were the strongest in these early and acute infections - due to dominant responses to a single epitope in each case (TW10 for B*57 and KK10 for B*27).
In the presence of HLA-B*57 and HLA-B*27 restricted responses, the relative contribution of other restricting HLA dropped greatly.

References

Altfeld2006 Marcus Altfeld, Elizabeth T. Kalife, Ying Qi, Hendrik Streeck, Mathias Lichterfeld, Mary N. Johnston, Nicole Burgett, Martha E. Swartz, Amy Yang, Galit Alter, Xu G. Yu, Angela Meier, Juergen K. Rockstroh, Todd M. Allen, Heiko Jessen, Eric S. Rosenberg, Mary Carrington, and Bruce D. Walker. HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1. PLoS Med., 3(10):e403, Oct 2006. PubMed ID: 17076553. Show all entries for this paper.

Displaying record number 54527

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	binding affinity, subtype comparisons, acute/early infection

Notes

T-cell responses to clade B Gag peptides were tested using sequences based on consensus (CON), most recent common ancestor (ANC) and center of tree (COT); as well as CON sequences from clade A, clade C and M-group Gag. It was found that Gag-specific cross-clade T-cell IFN-gamma responses are detectable during primary infection, and there was no significant difference in breadth or magnitude of responses with the different peptide sets. While several epitopes in low diversity domains are invariant across clades, other recognized variants are seen outside HLA anchor positions. T-cell immunity often tolerates conservative or semi-conservative amino acid substitutions but changes presumed to be in TCR contact sites may abrogate epitope recognition.
This epitope, KAFSPEVIPMF, is invariant across CON A, B, C and M-Group sequences, as well as clade B COT and ANC sequences. HLA-B57 restriction was inferred based on subject possessing appropriate HLA class I allele and prior publication

References

Malhotra2007 Uma Malhotra, Jessica Nolin, James I. Mullins, and M. Juliana McElrath. Comprehensive Epitope Analysis of Cross-Clade Gag-Specific T-Cell Responses in Individuals with Early HIV-1 Infection in the US Epidemic. Vaccine, 25(2):381-390, 4 Jan 2007. PubMed ID: 17112643. Show all entries for this paper.

Displaying record number 54871

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	vaccine-induced immune responses, characterizing CD8+ T cells

Vaccine Details

Vaccine type	canarypox, canarypox prime with recombinant protein boost
Vaccine strain	B clade BRU, B clade LAI, B clade MN, multiple epitope immunogen
Vaccine component	Gag, gp120, gp41, Nef, Pol, Protease

Notes

CD8+ T-cell function induced by HIV-1 immunogens and natural infection was compared. Natural infections consisted of early, chronic, and long term nonprogressors.
B27- and B57-restricted CD8+ T cells from nonprogressors exhibited greater expansion than those restricted by other alleles, providing an explanation for the observed association between HLA-B27/B57 and control of HIV-1 infection.

References

Horton2006 Helen Horton, Ian Frank, Ruth Baydo, Emilie Jalbert, Justin Penn, Sean Wilson, John P. McNevin, Matthew D. McSweyn, Deborah Lee, Yunda Huang, Stephen C. De Rosa, and M. Juliana McElrath. Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection. J. Immunol., 177(10):7406-7415, 15 Nov 2006. PubMed ID: 17082660. Show all entries for this paper.

Displaying record number 57598

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, genital and mucosal immunity

Notes

Rectal CD8+ T-cell responses to HIV Gag, Env and Nef were mapped at the peptide level in 4 groups: elite controllers, viremic controllers, non-controllers, and drug-treated subjects. In all patient groups, immunodominant responses were shared by blood and mucosa, with 2 exceptions. First, in HIV controllers, the magnitude of responses to B27- and B57-restricted epitopes was higher than responses to other alleles. Second, peptides recognized by T cells in both blood and mucosa elicited higher response than those recognized only by blood or only by mucosa.
Gag-specific responses, particularly to p24 and p7, dominated in controllers, while responses in non-controllers were more evenly distributed among Gag, Env, and Nef.
Peptides that included immunodominant epitope KAFSPEVIPMF were detected with high frequency in both controllers and non-controllers.
Epitope KAFSPEVIPMF had a median IFN-γ responses of 678 (blood) and 824 (mucosa) SFC/million.

References

Ferre2010 April L. Ferre, Donna Lemongello, Peter W. Hunt, Megan M. Morris, Juan Carlos Garcia, Richard B. Pollard, Hal F. Yee, Jr., Jeffrey N. Martin, Steven G. Deeks, and Barbara L. Shacklett. Immunodominant HIV-Specific CD8+ T-Cell Responses Are Common to Blood and Gastrointestinal Mucosa, and Gag-Specific Responses Dominate in Rectal Mucosa of HIV Controllers. J. Virol., 84(19):10354-10365, Oct 2010. PubMed ID: 20668079. Show all entries for this paper.

Displaying record number 57980

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	immunodominance, elite controllers

Notes

Immunodominant responses were identified from progressors and controllers. Epitope-specific CD8 T-cell lines from progressors and controllers had similar effector function profiles in intracellular cytokine staining assays. In contrast, CD8 T-cell lines derived from controllers showed enhanced virus suppression when compared with progressors. Virus suppression was mediated in an MHC-dependent manner and found to correlate with a polyfunctional IL-2+ CD8 T-cell response.
KAFSPEVIPMF was one of 15 immunodominant responses identified, and a T-cell line was isolated from a B57-positive controller patient who was highly responsive to it.

References

Akinsiku2011 Olusimidele T. Akinsiku, Anju Bansal, Steffanie Sabbaj, Sonya L. Heath, and Paul A. Goepfert. Interleukin-2 Production by Polyfunctional HIV-1-Specific CD8 T Cells Is Associated with Enhanced Viral Suppression. J. Acquir. Immune Defic. Syndr., 58(2):132-140, 1 Oct 2011. PubMed ID: 21637109. Show all entries for this paper.

Displaying record number 55108

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Australia, Canada, United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, escape, mutation acquisition, optimal epitope

Notes

To characterize HIV-1 proteome areas that are targeted in early, effective CTL responses, two cohorts were studied. Responses in early infection were against fewer epitopes and of lower magnitude than during chronic infection. While no region of the proteome was favored, Nef was the predominant target based on length of proteins.
When based on the expression of protective versus nonprotective HLA I alleles, it was found that HLA-B27 and -57 possessing slow progressors to disease directed the majority of their responses to Gag in early infection, as opposed to those with HLA-B*3501 or B*3502, i.e. rapid progressors to AIDS, who had negligible responses to Gag. As compared with HLA-B57-/B27- subjects and HLA-B35 subjects, HLA-B57+/27+ subjects responded most to the p24 component of Gag. By using overlapping peptides within Gag p24, two were picked as being consistently targeted, and both contained previously described epitopes TSTLQEQIGW and KRWIILGLNK.
IVLPEKDSW, i.e. epitope IW9 of RT protein was targeted in 62% of B57+ non-progressors to disease.

References

Streeck2007a Hendrik Streeck, Mathias Lichterfeld, Galit Alter, Angela Meier, Nickolas Teigen, Bader Yassine-Diab, Harlyn K. Sidhu, Susan Little, Anthony Kelleher, Jean-Pierre Routy, Eric S. Rosenberg, Rafick-Pierre Sekaly, Bruce D. Walker, and Marcus Altfeld. Recognition of a Defined Region within p24 Gag by CD8+ T Cells during Primary Human Immunodeficiency Virus Type 1 Infection in Individuals Expressing Protective HLA Class I Alleles. J. Virol., 81(14):7725-7731, Jul 2007. PubMed ID: 17494064. Show all entries for this paper.

Displaying record number 55163

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11 ?
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	South Africa, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	memory cells

Notes

Cohorts of HIV-infected subjects from the US and South Africa were screened for CD8+ EliSpot responses. Tetramer assays were performed for 13 frequently targeted HIV epitopes and compared to Flu, vaccinia, and EBV epitopes assayed in non-HIV-infected subjects. HIV tetramer+ CD8 T cells expressed less CD127, and this reduction was pervasive across all epitopes and alleles tested. These results indicated impaired HIV-specific memory CD8 T cell differentiation, regardless of level of control of viremia, epitopes targeted, or HLA alleles.

References

Wherry2006 E John Wherry, Cheryl L. Day, Rika Draenert, Joseph D. Miller, Photini Kiepiela, Tonia Woodberry, Christian Brander, Marylyn Addo, Paul Klenerman, Rafi Ahmed, and Bruce D. Walker. HIV-Specific CD8 T Cells Express Low Levels of IL-7Ralpha: Implications for HIV-Specific T Cell Memory. Virology, 353(2):366-373, 30 Sep 2006. PubMed ID: 16860834. Show all entries for this paper.

Displaying record number 55184

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Tetramer binding
Keywords	responses in children, rate of progression

Notes

A study of long-term surviving children in Kenya revealed CD8 T-cell responses in all progression groups. The most striking atttribute of long term surviving children was strong CD4 T-cell responses, which may be significant in delaying disease progression.
Response detected in 1 typically progressing child.

References

Chakraborty2005 Rana Chakraborty, Anne-Sophie Morel, Julian K. Sutton, Victor Appay, Ruth M. Ripley, Tao Dong, Tim Rostron, Simon Ogola, Tresa Palakudy, Rachel Musoke, Angelo D'Agostino, Mary Ritter, and Sarah L. Rowland-Jones. Correlates of Delayed Disease Progression in HIV-1-Infected Kenyan Children. J. Immunol., 174(12):8191-8199, 15 Jun 2005. PubMed ID: 15944328. Show all entries for this paper.

Displaying record number 55613

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction

Notes

Peptide prediction programs based on MHC binding, proteasomal cleavage and TAP transport were applied to select novel epitopes absent from the Los Alamos HIV database. 22 novel epitopes were tested by IFN-gamma ELISpot and 19 (11 HLA-B27 restricted, 8 HLA-B57 restricted) induced strong positive responses.
Magnitude of response generated was similar to that of previously identified epitopes, but the number of individuals responding was lower. This could be explained by less stringent HLA-typing of subjects and perhaps high sequence variability within these novel epitopes.
KF11, KAFSPEVIPMF, is a known HLA-B57-restricted epitope used as a positive control for eliciting CTL IFN-gamma response.

References

Schellens2008 Ingrid M. M. Schellens, Can Kesmir, Frank Miedema, Debbie van Baarle, and José A. M. Borghans. An Unanticipated Lack of Consensus Cytotoxic T Lymphocyte Epitopes in HIV-1 Databases: The Contribution of Prediction Programs. AIDS, 22(1):33-37, 2 Jan 2008. PubMed ID: 18090389. Show all entries for this paper.

Displaying record number 57978

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	immunodominance, elite controllers

Notes

Immunodominant responses were identified from progressors and controllers. Epitope-specific CD8 T-cell lines from progressors and controllers had similar effector function profiles in intracellular cytokine staining assays. In contrast, CD8 T-cell lines derived from controllers showed enhanced virus suppression when compared with progressors. Virus suppression was mediated in an MHC-dependent manner and found to correlate with a polyfunctional IL-2+ CD8 T-cell response.
KAFSPEVIPMF was one of 15 immunodominant responses identified, and a T-cell line was isolated from a B57-positive controller patient who was highly responsive to it.

References

Displaying record number 57974

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	immunodominance, elite controllers

Notes

Immunodominant responses were identified from progressors and controllers. Epitope-specific CD8 T-cell lines from progressors and controllers had similar effector function profiles in intracellular cytokine staining assays. In contrast, CD8 T-cell lines derived from controllers showed enhanced virus suppression when compared with progressors. Virus suppression was mediated in an MHC-dependent manner and found to correlate with a polyfunctional IL-2+ CD8 T-cell response.
KAFSPEVIPMF was one of 15 immunodominant responses identified, and a T-cell line was isolated from a B57-positive progressor patient who was highly responsive to it.

References

Displaying record number 56308

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172 SF2, HXBc2/Bal R5)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A2, B40, B57, Cw3, Cw6
Country	United States
Experimental methods	Cytokine production, Degranulation, CD107a and b cell surface mobilization, Flow cytometric T-cell cytokine assay
Keywords	supervised treatment interruptions (STI), immunodominance, characterizing CD8+ T cells, drug resistance

Notes

A detailed analysis of 6 chronically infected patients' CTL responses to autologous virus was performed after ART and SIT (structured interruption of therapy). Qualitative responses including degranulation and production of IFN-gamma, MIP-1beta, TNF-alpha, IL-2, but not memory CD27, CD45RO and CD57 T cells correlated with extended low plasma viremia. Frequency and breadth of CTL response as well as immune escape did not influence virological outcome.
One patient exhibited drug resistance mutations K170R (to NNRTI efavirenz) and D76N, K70R (to NRTIs).
Autologous epitopes were preferentially recognized over optimal, consensus sequences.
Patients with favorable virological outcomes demonstrated CTL recognition within multiple, conserved regions of Gag and Nef.
Patients with poor virological outcomes recognized optimal epitopes with much lower frequencies, though this was not significant.
HLA-B57-restricted epitope, KAFSPEVIPMF, elicited a response in 1 patient and is found in Gag immunodominant region EKAFSPEVIPMFSAL.

References

Daucher2008 Marybeth Daucher, David A. Price, Jason M. Brenchley, Laurie Lamoreaux, Julia A. Metcalf, Catherine Rehm, Elizabeth Nies-Kraske, Elizabeth Urban, Christian Yoder, Diane Rock, Julie Gumkowski, Michael R. Betts, Mark R. Dybul, and Daniel C. Douek. Virological Outcome after Structured Interruption of Antiretroviral Therapy for Human Immunodeficiency Virus Infection Is Associated with the Functional Profile of Virus-Specific CD8+ T Cells. J. Virol., 82(8):4102-4114, Apr 2008. PubMed ID: 18234797. Show all entries for this paper.

Displaying record number 57839

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, TCR binding
Keywords	rate of progression, TCR usage, optimal epitope

Notes

The study measured the functional avidities of HIV-specific CTL responses targeting 20 optimally defined CTL epitopes in a cohort of 44 HIV controllers and 68 non-controllers. Highest functional avidities were toward HLA-B-restricted epitopes in Gag. Avidities were higher in HIV controllers than non-controllers. Higher-avidity T-cell populations had narrower TCR repertoires.
KAFSPEVIPMF was one of 20 optimal epitopes tested.
Responses to B27-KK10 and B57-KF11 showed higher functional avidities than other responses studied.

References

Berger2011 Christoph T. Berger, Nicole Frahm, David A. Price, Beatriz Mothe, Musie Ghebremichael, Kari L. Hartman, Leah M. Henry, Jason M. Brenchley, Laura E. Ruff, Vanessa Venturi, Florencia Pereyra, John Sidney, Alessandro Sette, Daniel C. Douek, Bruce D. Walker, Daniel E. Kaufmann, and Christian Brander. High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control. J. Virol., 85(18):9334-9345, Sep 2011. PubMed ID: 21752903. Show all entries for this paper.

Displaying record number 57688

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Germany, United States
Experimental methods	Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	memory cells

Notes

CTL effector-memory differentiation (i.e. presence of CD45RO+/CCR7- or CD45RA+/CCR7- CTL) was studied in relation to 2 surface expression markers, CD45RO+/CCR7- (TemRA) and CD57. HIV-1-specific CTL with TemRA expression form an under-represented population of total TemRA+ CTL; but in subjects with slow progression to disease, a large proportion of their HIV-1-specific CTL are TemRA+. This shows HIV-1-specific CTL differentiation to be TCR-dependent with respect to the marker TemRA. For CD57+ CTL however, maturation was TCR-independent since senescence marker CD57 surface expression was similar for (i) different clonotypes targeting the same HIV-1 epitope (ii) epitope-specific CTL clonotypes at varied stages of differentiation. Thus both TCR-dependent and -independent development of CTL are important for their effector-memory repertoire.
TCRB clonotype distribution between TemRA and TemRO phenotypes of CTL suggest that differentiation is simultaneous from naive CTL to either TemRA or TemRO CTL compartments. This study was conducted on epitope KF11-specific CTL in HLA-B57 subject 10076.
Differentiation into the TemRA memory phenotype was shown to be selective and variable, driven by the selective expansion of distinct TCR clonotype populations within HIV-1-specific CTL populations. FL8-specific- and KK10-specific-memory-CTL in subject 10022 are composed of varying percentages of different TRBV expressions. FL8-specific memory CTL in subject 10071 also express 3 different TRBV genes, resulting in differing proportions of 3 different memory CTL sub-populations.
HLA-B57 restricted CTL specific against epitope KF11 were studied by Tetramer staining and flow cytometry. TemRO, TemRA and memory cells against this epitope were followed.
Other epitopes to which CTL were detected were B15-TY11, B15-GY10, B57-QW9, B15-QW9, A3-RK9 and B8-EI8.

References

Meyer-Olson2010 Dirk Meyer-Olson, Brenna C. Simons, Joseph A. Conrad, Rita M. Smith, Louise Barnett, Shelly L. Lorey, Coley B. Duncan, Ramesh Ramalingam, and Spyros A. Kalams. Clonal Expansion and TCR-Independent Differentiation Shape the HIV-Specific CD8+ Effector-Memory T-Cell Repertoire In Vivo. Blood, 116(3):396-405, Jul 22 2010. PubMed ID: 20424187. Show all entries for this paper.

Displaying record number 52194

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57, B58)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

Neisseria gonorrhea cervititis in 9 HIV+ Kenyan sex workers caused a functional deficiency in IFN-gamma production in HIV-1 epitope-specific CD8+ T-cells, detected by intracellular cytokine production and tetramer assays, while not affecting the total number of epitope-specific CTLs.
Ghonorrhea caused the weaker HIV-1 specific CTL responses in 4 HIV-1 exposed persistently seronegative (HEPS) women to become undetectable by Elispot and tetramer assays, and CMV-specific CTL in 2 HEPS subjects were shown to have impaired function with regard to IFN-gamma production.

References

Kaul2002 Rupert Kaul, Sarah L. Rowland-Jones, Geraldine Gillespie, Joshua Kimani, Tao Dong, Peter Kiama, J. Neil Simonsen, Job J. Bwayo, Andrew J. McMichael, and Francis A. Plummer. Gonococcal Cervicitis is Associated with Reduced Systemic CD8+ T Cell Responses in Human Immunodeficiency Virus Type 1-Infected and Exposed, Uninfected Sex Workers. J. Infect. Dis., 185(10):1525-1529, 15 May 2002. PubMed ID: 11992292. Show all entries for this paper.

Displaying record number 1695

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(153-164)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B57, B58)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS), immunodominance

Notes

ELISPOT was used to study CTL responses to a panel of 54 predefined HIV-1 epitopes in 91 HIV-1-exposed, persistently seronegative (HEPS) and 87 HIV-1-infected female Nairobi sex workers.
Responses in HEPS women tended to be lower, and focused on different epitopes with HLA presenting molecules that have previously been associated with reduced risk of infection, and there was a shift in the response in the HEPS women upon late seroconversion to epitopes recognized by the HIV-1 infected women.
43/91 HEPS women had CD8+ responses and detection of HIV-1-specific CTL in HEPS women increased with the duration of viral exposure.
Among HLA-B57/B58 women, 4/6 HEPS and 12/17 HIV-1 infected women recognized this epitope.
The dominant response to this HLA allele was to this epitope in 2 of the 4/6 HEPS cases and in 7 of the 12/17 HIV-1 infected women.

References

Kaul2001a R. Kaul, T. Dong, F. A. Plummer, J. Kimani, T. Rostron, P. Kiama, E. Njagi, E. Irungu, B. Farah, J. Oyugi, R. Chakraborty, K. S. MacDonald, J. J. Bwayo, A. McMichael, and S. L. Rowland-Jones. CD8(+) lymphocytes respond to different HIV epitopes in seronegative and infected subjects. J. Clin. Invest., 107(10):1303-10, May 2001. URL: http://www.jci.org/cgi/content/full/107/10/1303. PubMed ID: 11375420. Show all entries for this paper.

Displaying record number 53642

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B*5801, B57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	responses in children, mother-to-infant transmission, escape, characterizing CD8+ T cells

Notes

Escape mutations in TW10 and other B57-restricted epitopes were shown to arise early in infants following perinatal infection. Some escape variants were likely to have been transmitted vertically, from HLA-B57/5801 positive HIV-1 infected mothers, while others arose during infancy in cases where the children inherited the B57/5801 allele paternally. In contrast to adults, the majority of children showed a robust response to the escape variants, suggesting that infants are able to mount functional immune responses and drive immune escape and that a developing immune system may exhibit greater plasticity in recognizing viral variants.
KAFSPEVIPMF was frequently recognized in children and in adults.

References

Feeney2005a Margaret E. Feeney, Yanhua Tang, Katja Pfafferott, Kathleen A. Roosevelt, Rika Draenert, Alicja Trocha, Xu G. Yu, Cori Verrill, Todd Allen, Corey Moore, Simon Mallal, Sandra Burchett, Kenneth McIntosh, Stephen I. Pelton, M. Anne St. John, Rohan Hazra, Paul Klenerman, Marcus Altfeld, Bruce D. Walker, and Philip J. R. Goulder. HIV-1 Viral Escape in Infancy Followed by Emergence of a Variant-Specific CTL Response. J. Immunol., 174(12):7524-7530, 15 Jun 2005. PubMed ID: 15944251. Show all entries for this paper.

Displaying record number 56751

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	( pMJ5)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B*5801, B57)
Immunogen	in vitro stimulation or selection
Experimental methods	Relative replication capacity assay
Keywords	escape, viral fitness and reversion

Notes

The study examined 3 B57/B5801-associated escape mutations in the capsid protein and measured their effect on viral replication capacity. The well-documented antiretroviral drug resistance escape mutation M184V was used as the basis of comparison. Singly, each escape mutant had an effect on replication capacity that was similar to M184V. Coexpression resulted in further reduction of replication capacity. Thus the costs of escape are sufficient to affect in vivo viral dynamics.
The A163G escape mutant of KF11 had a relative viral replication capacity of 0.89 compared to wild type virus. The triple mutant of A146P, A163G and T242N had a relative replication capacity of 0.62.

References

Boutwell2009 Christian L Boutwell, Christopher F Rowley, and M Essex. Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein. J Virol, 83(6):2460-8, Mar 2009. PubMed ID: 19109381. Show all entries for this paper.

Displaying record number 53655

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human(B57, B63)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, HLA cross-presentation, optimal epitope

Notes

HLA-B63-positive subjects were shown to be able to generate CTL responses early in acute HIV infection and to control HIV replication in the absence of antiretroviral treatment. Since HLA-B63 shares the epitope binding motif of HLA-B57 and -B58, it was shown that HLA-B63-positive individuals mounted CTL responses to previously identified B57-restricted epitopes, as well as novel, B63-restricted epitopes. Moreover, these novel B63-restricted epitopes can also be presented by HLA-B57 and -B58.
This epitope was recognized by 60% of B63-positive subjects and 33% of B57/58-positive subjects.

References

Frahm2005a Nicole Frahm, Sharon Adams, Photini Kiepiela, Caitlyn H. Linde, Hannah S. Hewitt, Mathias Lichterfeld, Kaori Sango, Nancy V. Brown, Eunice Pae, Alysse G. Wurcel, Marcus Altfeld, Margaret E. Feeney, Todd M. Allen, Timothy Roach, M. Anne St. John, Eric S. Daar, Eric Rosenberg, Bette Korber, Francesco Marincola, Bruce D. Walker, Philip J. R. Goulder, and Christian Brander. HLA-B63 Presents HLA-B57/B58-Restricted Cytotoxic T-Lymphocyte Epitopes and Is Associated with Low Human Immunodeficiency Virus Load. J. Virol., 79(16):10218-10225, Aug 2005. PubMed ID: 16051815. Show all entries for this paper.

Displaying record number 59165

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	gag 162-172
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, HLA binding, Intracellular cytokine staining, Other
Keywords	binding affinity, elite controllers

Notes

49 HLA-B*57⁺ and 52 HLA-B*57^- ART-naive HIV controllers (HIC) from the French ANRS CODEX cohort were compared to determine various impacts of B*57 and non-B*57 alleles on HIV-specific CTL responses (e.g. activation and differentiation markers, proliferation potential, cytokine production and HIV-suppression). HLA-B*57⁺ chronic progressors were the control group.
CTL response was higher in HLA-B*57⁺ than -B*57^- subjects, most of them Gag-specific. 80% of all such responses were restricted by -B*57^- Gag or Nef epitopes.
Greater frequency of as well as stronger CTL responses correlated with higher functional avidity of TCR-peptide interaction. B*57-restricted responses were 1 log more sensitive than non-B*57-restricted responses regardless of whether subjects were HLA-B*57⁺ or -B*57^-, and led to higher proliferation of CTL, higher IL-2 production, higher frequency of IFN-γ-producing cells, higher degree of differentiation with more CD127 (and as seen by higher markers for central memory cells, CCR7⁺CD45RO⁺ / effector memory cells, CCR7⁺CD27⁺CD45RO⁺ / senescent cells, CD57⁺). Activation markers CD38 and HLA-DR however, remained the same between CTL restricted by HLAs -B*57 or not.
Higher TCR-peptide avidity was correlated also to HICs as compared to progressors - with proliferation, IL-2 production and CD127 levels being affected in HLA-B*57-restricted responding CTL.
Viral replication suppression was seen in all HIC whether HLA-B*57⁺ or -B*57^-. Strong viral suppression (SVS) correlates with lower plasma viral load.
HLA-B*5701-restricted peptide gag 162-172, KAFSPEVIPMF, was recognized by 38/48 B*57⁺ subjects, with a mean intensity ˜1000 Sfc/10⁶ PBMCs.

References

Lecuroux2014 Camille Lécuroux, Asier Sáez-Cirión, Isabelle Girault, Pierre Versmisse, Faroudy Boufassa, Véronique Avettand-Fenoël, Christine Rouzioux, Laurence Meyer, Gianfranco Pancino, Olivier Lambotte, Martine Sinet, and Alain Venet. Both HLA-B*57 and Plasma HIV RNA Levels Contribute to the HIV-Specific CD8+ T Cell Response in HIV Controllers. J. Virol., 88(1):176-187, Jan 2014. PubMed ID: 24131719. Show all entries for this paper.

Displaying record number 52086

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, immunodominance

Notes

CTL activity was monitored in 27 individuals, including 10 LTNP with an over-expression of HLA B*5701 -- these individuals have viral loads below the threshold of infection without therapy, and their immune response tends to be focused on peptides that contain B*5701 epitopes ISPRTLNAW, KAFSPEVIPMF, TSTLQEQIGW, and QASQEVKNW.
CTL responses are broader in B*5701+ individuals with progressive viremia than those that control viremia.
The HLA-A*0201 SLYNTVATL epitope response was not as strong in individuals that carried both A2 and B57.

References

Migueles2001 Stephen A. Migueles and Mark Connors. Frequency and Function of HIV-Specific CD8(+) T Cells. Immunol. Lett., 79(1-2):141-150, 1 Nov 2001. PubMed ID: 11595301. Show all entries for this paper.

Displaying record number 59208

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Patient MHC/HLA	P1: B5701; P6: B5701
Country	United States
Experimental methods	Other
Keywords	elite controllers

Notes

Variations at 4 Gag and 2 Nef epitopes in 6 B*5701+ ART-naive males from the Options cohort - 3 high-risk progressors (HRPs) and 3 very low-risk progressors (LRPs) - were tested for correlation to polyfunctional T cell responses. Subjects were followed from infection to 7 years post-infection and 6 markers (IFN-γ, IL-2, MIP-1β, TNF, CD107a and perforin) were measured. While LRPs maintained a directed functional response against emerging variants, emerging epitopes in HRPs correlated with a decrease in IL-2-producing cells, functional avidity and polyfunctional sensitivity.
Variants (KAFSPEVIPMs, KAFSPEiIPMF, KAFSPEVIPMt, KAsSPEVIPMF) of KAFSPEVIPMF, KF11, were seen in 1/3 LRPs and 1/3 HRPs, over 3 time points. Magnitude of response as seen to KF11 was not a predictive factor for emergence of variants.

References

Buggert2014 Marcus Buggert, Melissa M. Norström, Marco Salemi, Frederick M. Hecht, and Annika C. Karlsson. Functional Avidity and IL-2/Perforin Production Is Linked to the Emergence of Mutations within HLA-B*5701-Restricted Epitopes and HIV-1 Disease Progression. J. Immunol., 192(10):4685-4696, 15 May 2014. PubMed ID: 24740510. Show all entries for this paper.

Displaying record number 52082

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, immunodominance

Notes

HLA B*5701 was found in a very high frequency in HIV-1 infected non-progressors, 11/13 (85%) versus 19/200 (9.5%) of progressors. Non-progressors tended to have an immune response that was highly focused on four p24 epitopes that were presented by B*5701, ISPRTLNAW, KAFSPEVIPMF, TSTLQEQIGW, and QASQEVKNW.
Attempts to make all for HLA B*5701-epitope tetramers were made, but only the HLA B*5701-KAFSPEVIPMF tetramer folded properly. The percentage of CD8+ T cells staining with this HLA B*57 gag tetramer and the fraction of CD69+IFN-+ cells responding to autologous B cells pulsed with KAFSPEVIPMF was highly correlated (r = 0.84; P = 0.005). The percent of CD8+ T cells that stain with the A*2 gag SLYNTVATL tetramer was low (0-0.31%) in a A2+ B57+ LTNP, emphasizing the focus of the immune response on the B*5701 epitopes.

References

Displaying record number 52760

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KAF11
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods	Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	rate of progression, escape

Notes

cDNA Gag sequences from a set of 17 HLA-B*5701+ progressors and 10 LTNPs were obtained, and the variation in four p24 B*5701 epitopes examined. Sequence variants were more common (p < 0.01) in the epitopes in the progressors (median 3, range 1-7) than LTNPs (median 2, range 0-4).
In general, use of the autologous protein in a target cell did not diminish the overall CD8+ T-cell responses.
This epitope tends to be quantitatively immunodominant in B57+ people, including in some of the individuals in this study. It was extremely well conserved in the sequences obtained here, despite strong immune pressure, suggesting fitness constraints.

References

Migueles2003 Stephen A. Migueles, Alisha C. Laborico, Hiromi Imamichi, W. Lesley Shupert, Cassandra Royce, Mary McLaughlin, Linda Ehler, Julia Metcalf, Shuying Liu, Claire W. Hallahan, and Mark Connors. The Differential Ability of HLA B*5701+ Long-Term Nonprogressors and Progressors to Restrict Human Immunodeficiency Virus Replication Is Not Caused by Loss of Recognition of Autologous Viral gag Sequences. J. Virol., 77(12):6889-6898, Jun 2003. PubMed ID: 12768008. Show all entries for this paper.

Displaying record number 62172

HXB2 Location	Gag(162-172) p24(30-40)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods	HLA binding
Keywords	binding affinity, NK cells

Notes

A modifier in the protective role of HLA-B*57 has been found. Single variant I47V in a surface-expressed immune NK cell receptor, KIR3DL1, that binds HLA-B*5701 can enhance its, but not other related HLA like B*5703's, protective role. This rs643347G/A variant in the DO domain is enriched in B*57+-controllers. A combination of variants at KIR3DL1 positions 2, 47, and 54 could modulate B*57-mediated protection from HIV-1.
The KIR3DL1 makes contact and clusters with 2 HLA molecules, but the sites of mutation are far from the ligand-binding site. Surface plasmon resonance was used to measure the binding affinities of different KIR3DL1s to B*5701-Gag epitopes. No significant difference was detected in binding of KIR3DL1*015 or *001 to B*57-KF11.

References

Martin2018 Maureen P. Martin, Vivek Naranbhai, Patrick R. Shea, Ying Qi, Veron Ramsuran, Nicolas Vince, Xiaojiang Gao, Rasmi Thomas, Zabrina L. Brumme, Jonathan M. Carlson, Steven M. Wolinsky, James J. Goedert, Bruce D. Walker, Florencia P. Segal, Steven G. Deeks, David W. Haas, Stephen A. Migueles, Mark Connors, Nelson Michael, Jacques Fellay, Emma Gostick, Sian Llewellyn-Lacey, David A. Price, Bernard A. Lafont, Phillip Pymm, Philippa M. Saunders, Jacqueline Widjaja, Shu Cheng Wong, Julian P. Vivian, Jamie Rossjohn, Andrew G. Brooks, and Mary Carrington. Killer Cell Immunoglobulin-Like Receptor 3DL1 Variation Modifies HLA-B*57 Protection against HIV-1. J. Clin. Invest., 128(5):1903-1912, 1 May 2018. PubMed ID: 29461980. Show all entries for this paper.

Displaying record number 57996

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Country	South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	computational epitope prediction, optimal epitope

Notes

A prediction tool, HLArestrictor, was developed to predict minimal epitopes from longer peptides. Minimal epitopes were predicted and validated for 18 EliSpot-positive 18mers.
KAFSPEVIPMF was predicted from EliSpot-positive 18mer WVKVIEEKAFSPEVIPMF. The epitope was validated in two B*5701-positive HIV-positive individuals by tetramer staining.

References

ErupLarsen2011 Malene Erup Larsen, Henrik Kloverpris, Anette Stryhn, Catherine K. Koofhethile, Stuart Sims, Thumbi Ndung'u, Philip Goulder, Søren Buus, and Morten Nielsen. HLArestrictor---A Tool for Patient-Specific Predictions of HLA Restriction Elements and Optimal Epitopes within Peptides. Immunogenetics, 63(1):43-55, Jan 2011. PubMed ID: 21079948. Show all entries for this paper.

Displaying record number 55001

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KAF
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	rate of progression, TCR usage, variant cross-reactivity

Notes

Functional cross-reactivity of CD8 responses to HIV-1 epitopes restricted by different HLA-alleles was analyzed. It was shown that epitope-specific responses with the most efficient cross-recognition were strongly associated with delayed disease progression. Variant-cross recognition efficiency was linked to the dominant TCRs used for epitope recognition. Epitopes restricted by the same HLA-allele did not show similar variant cross-recognition efficiency, suggesting that the rate of disease progression might be associated with the quality of responses to certain critical epitopes.
This epitope, B57-KAF that is strongly associated with delayed progression to AIDS and its natural as well as alanine-substituted variants are efficiently cross-recognized. At lower peptide concentrations, efficiency of variant cross-recognition was reduced, even while interepitopic differences in variant cross-recognition efficiency were maintained. CTLs responding to this epitope expressed the same predominant TCR Vbeta family, but individuals whose CTLs predominantly used TCR Vbeta 17 had less efficient variant cross-reactivity.

References

Turnbull2006 Emma L. Turnbull, A. Ross Lopes, Nicola A. Jones, David Cornforth, Phillipa Newton, Diana Aldam, Pierre Pellegrino, Jo Turner, Ian Williams, Craig M. Wilson, Paul A. Goepfert, Mala K. Maini, and Persephone Borrow. HIV-1 Epitope-Specific CD8+ T Cell Responses Strongly Associated with Delayed Disease Progression Cross-Recognize Epitope Variants Efficiently. J. Immunol., 176(10):6130-6146, 15 May 2006. PubMed ID: 16670322. Show all entries for this paper.

Displaying record number 57914

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B*5701)
Immunogen	peptide-HLA interaction
Experimental methods	Tetramer binding
Keywords

Notes

The study investigated whether HLA-Bw4-presented peptides could affect the interaction between the HLA and natural killer cell receptor KIR3DL1. Various HIV-1 epitopes differentially modulated the binding of KIR3DL1 to HLA-Bw4.
Bw4(B*5701)-restricted epitope KAFSPEVIPMF bound weakly to KIR3DL1.

References

Fadda2011 Lena Fadda, Geraldine M. O'Connor, Swati Kumar, Alicja Piechocka-Trocha, Clair M. Gardiner, Mary Carrington, Daniel W. McVicar, and Marcus Altfeld. Common HIV-1 Peptide Variants Mediate Differential Binding of KIR3DL1 to HLA-Bw4 Molecules. J Virol, 85(12):5970-5974, Jun 2011. PubMed ID: 21471246. Show all entries for this paper.

Displaying record number 54745

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B*5701)
Immunogen	peptide-HLA interaction
Experimental methods	Tetramer binding
Keywords	binding affinity

Notes

MHC can exert a protective effect on HIV-1 disease progression by the interaction of MHC Class I molecules with Killer Inhibitory Receptors (KIR) of the innate immune system. Here, KIR3DS1, a putative stimulatory receptor and allele of the inhibitory KIR3DL1, is studied. Bw4 MHC Class I proteins were implicated in this KIR's ligand specificity, but the authors were unable to generate binding of Bw4Ile80 tetramers in complex with epitopes to KIR3DS1 transiently expressed on 293-T cells, using a panel of HIV-epitopes differing at p7 and p8.
This epitope, KAFSPEVIPMF (MHC Class I restriction, serotype Bw4Ile80) complexed with MHC B*5701 as a tetramer was unable to bind KIR3DS1 at 4, 20 and 37C. However, the complex B*57-KAFSPEVIPMF does bind inhibitory KIR3DL1 subtype KIR3DL1*005.

References

Gillespie2007 Geraldine M. A. Gillespie, Arman Bashirova, Tao Dong, Daniel W. McVicar, Sarah L. Rowland-Jones, and Mary Carrington. Lack of KIR3DS1 Binding to MHC Class I Bw4 Tetramers in Complex with CD8+ T Cell Epitopes. AIDS Res. Hum. Retroviruses, 23(3):451-455, Mar 2007. PubMed ID: 17411378. Show all entries for this paper.

Displaying record number 58676

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172 NL4-3)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Patient MHC/HLA	R039: A0101, A3101, B2705, B5701, Cw0202, Cw0602
Country	United Kingdom
Experimental methods	Intracellular cytokine staining, Other
Keywords	acute/early infection

Notes

Antigen presentation kinetics of 2 protective Gag epitopes (HLA B*5701 restricted KAFSPEVIPMF, KF11, and HLA B*2705-restricted KRWIILGLNK, KK10) were compared to 2 non-immunodominant epitopes (Pol KRKGGIGGY, KY9, and Vpr VRHFPRIWL, VL9, both B*2705-restricted) during one cycle of replication. All but VL9 showed early epitope presentation due to early incoming HIV-1 particles, resulting in rapid CTL activation and infected cell clearance. Early presented epitopes correlated with a higher viral inoculum and elicited greater CTL activation. Results also substantiated the importance of using virus-infected cells for in vitro studies over peptide pulsing.
KF11 was presented early at 3-6 hours, followed by a later activation boost at 18h post infection. Its presentation does not depend on de novo synthesis of viral proteins during replication, but on incoming, infecting viral particles. A 10-fold decrease in the amount of virus inoculum resulted in a 2-3 fold decrease in % activated CTL.
Comparison of in vitro KF11 peptide pulsing studies to HIV-VLP (virus-like particle) infection of the epitope suggests that the former is at nonphysiological concentrations, 10³ to 10⁵ times higher than actual intracellular processed epitopes, resulting in higher magnitude of CTL activation and polyfunctional profile of cytokine secretion that may mask actual in vivo levels.

References

Kloverpris2013 Henrik N. Kløverpris, Rebecca P. Payne, Jonah B. Sacha, Jane T. Rasaiyaah, Fabian Chen, Masafumi Takiguchi, Otto O. Yang, Greg J. Towers, Philip Goulder, and Julia G. Prado. Early Antigen Presentation of Protective HIV-1 KF11Gag and KK10Gag Epitopes from Incoming Viral Particles Facilitates Rapid Recognition of Infected Cells by Specific CD8+ T Cells. J. Virol., 87(5):2628-2638, Mar 2013. PubMed ID: 23255798. Show all entries for this paper.

Displaying record number 162

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172 LAI)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression

Notes

This peptide was recognized by CTL from five slow progressors.
Peptide defined on the basis of B*5801 binding motif, yet not cross-restricted except at high concentrations.
This epitope is highly conserved.

References

Goulder1996 P. J. R. Goulder, M. Bunce, P. Krausa, K. McIntyre, S. Crowley, B. Morgan, A. Edwards, P. Giangrande, R. E. Phillips, and A. J. McMichael. Novel, Cross-Restricted, Conserved and Immunodominant Cytotoxic T Lymphocyte Epitopes in Slow HIV Type 1 Infection. AIDS Res. Hum. Retroviruses, 12:1691-1698, 1996. HLA-B*57 is over-represented in slow progressors. HLA*5801 is a closely related molecule, and while the defined anchor residues of HLA*5801 can be used to predict epitopes in HIV-1 proteins, the CTL from HLA-B*57 positive individuals have limited cross-presentation capacity with HLA*5801 targets. In this paper five new HLA-B*57 epitopes were defined. PubMed ID: 8959245. Show all entries for this paper.

Displaying record number 163

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172 LAI)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes this is a B*5701 epitope.

References

Llano2019 Anuska Llano, Samandhy Cedeño, Sandra Silva Arrieta, and Christian Brander. The 2019 Optimal HIV CTL Epitopes Update: Growing Diversity in Epitope Length and HLA restriction. 2019. Show all entries for this paper.

Displaying record number 58840

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Patient MHC/HLA	A0101, A0301, B2705, B5701; A0101, A2402, B4002, B5701; A2402, A3201, B4002, B5701; A0101, A0201, B5101, B5701; A0101, A0101, B0801, B5701; A0301, A2402, B3501, B5701
Country	United States
Experimental methods	Flow cytometric T-cell cytokine assay
Keywords	rate of progression

Notes

High resolution evolutionary and immunological data were used to follow 6 ART-naive, HLA-B*5701 positive subjects longitudinally over 7 years. Low risk progressors (LRPs) had more polyfunctional CTL responses to both TW10 (TSTLQEQIGW) and QW9 (QASQEVKNW) epitopes and produced early IL-2, resulting in higher, defining CD4+ baseline counts. Conversely, high risk progressors (HRPs) had more substitutions, less polyfunctionality of CTL response, resulting in lower CD4+ baseline counts.
Substitutions occurred more frequently in flanking regions of HLA-B*5701-restricted epitopes than within and this was true of both LRPs and HRPs.
Immunodominant epitope KF11 (E|KAFSPEVIPMF|S) was conserved in 4/6 subjects. Patients 1 and 6 (P1, P6) developed mutations in KF11 during chronic infection and most of the viral population contained V168I by the weeks post-infection point sampled.

References

Norstrom2012 Melissa M. Norström, Marcus Buggert, Johanna Tauriainen, Wendy Hartogensis, Mattia C. Prosperi, Mark A. Wallet, Frederick M. Hecht, Marco Salemi, and Annika C. Karlsson. Combination of Immune and Viral Factors Distinguishes Low-Risk Versus High-Risk HIV-1 Disease Progression in HLA-B*5701 Subjects. J. Virol., 86(18):9802-9816, Sep 2012. PubMed ID: 22761389. Show all entries for this paper.

Displaying record number 58963

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B*5701)
Immunogen	HIV-1 infection
Patient MHC/HLA	21746: A0101, A4801, B4001, B5701, Cw0304, Cw0602; 10849: A2301, A6801, B3543, B5703, Cw0102, Cw0210; 67200: A0101, A2401, B0801, B5701, Cw0602, Cw0701
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The extent to which set-point viremia is affected by early HIV-infection T cell responses to either conserved or variable epitopes was studied. 23 ART-naive subjects were characterized for CTL responses for 6 months, postinfection. While most CTL responses (73/123) were targeted against variable HIV-1 epitopes, recognition of conserved epitopes (16/123) was associated with lower set point viremia. This was independent of HLA type and also functional avidity of the CTL response. Most of the conserved responses were targeted to Gag and Pol epitopes.
4/16 conserved epitopes were restricted by favorable HLA alleles, and 3 of those 4 were recognized in all subjects possessing the favorable allele. Only one conserved epitope was recognized by an unfavorable allele.
KF11, KAFSPEVIPMF, restricted by favorable allele HLA-B*5701, was one of the conserved epitopes that was recognized in all B*57+ subjects - patients 67200 (A*01:01, 24G1; B*08:01, 57:01; C*06:02, 07G1), 10849 (A*23:01, 68G1; B*3543, 57:03; C*01:02, 02:10) and 21746 (A*01:01; 48:01; B*40:01, 57:01; C*03:04, 06:02).

References

Kunwar2013 Pratima Kunwar, Natalie Hawkins, Warren L. Dinges, Yi Liu, Erin E. Gabriel, David A. Swan, Claire E. Stevens, Janine Maenza, Ann C. Collier, James I. Mullins, Tomer Hertz, Xuesong Yu, and Helen Horton. Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design. PLoS One, 8(5):e64405, 2013. PubMed ID: 23741326. Show all entries for this paper.

Displaying record number 61576

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B5701, B5702, B*5703)
Immunogen	vaccine
Experimental methods	Other
Keywords	review, vaccine-induced immune responses, vaccine antigen design, protective allele

Notes

This review refocuses attention on host protective HLA/ MHC class I molecules after the failure of the 2007 Merck & Co. Inc. as well as the impending 2008 VRC vaccines.
Gag epitope KAFSPEVIPMF is associated with slow progression and low viral set point([Goulder et al. ARHR 12:1691-1698(1996)]; [Kaslow et al. Nature Med. 2:405-411 (1996)]; [O'Brien et al. Trends Mol. Med. 7:379-381(2001)]; [Migueles et al. PNAS 97: 2709-2714(2000)]; [Tang et. al. JVI 76:8276-8284 (2002)]; [Lazaryan et al. JVI 80:6056-6060 (2006)]).

References

Goulder2008 Philip J. R. Goulder and David I. Watkins. Impact of MHC Class I Diversity on Immune Control of Immunodeficiency Virus Replication. Nat. Rev. Immunol., 8(8):619-630, Aug 2008. PubMed ID: 18617886. Show all entries for this paper.

Displaying record number 54625

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, escape, HLA associated polymorphism, elite controllers

Notes

To study whether CTL responses restricted by "good" HLA I molecules exert stronger immune selection than other HLA I molecules, 54 and 70 optimal epitopes within HIV-1 Gag, Pol and Nef genes for Caucasian and African cohorts were tested in patients over a mean of 14 months. "Good", advantageous HLA allele-restricted epitopes were much more polymorphic than epitopes restricted by other, non-advantageous HLA in patients, suggesting that benefits associated with HLA Class I alleles of elite controllers of disease progression are epitope-specific. Such "driver" epitopes with high polymorphism had high frequency of immune response, allowing them to be ranked for recognition and polymorphism.
Patients with higher proportions of mutated epitopes also had lower plasma viral loads, and mean epitope variability correlated negatively with relative hazard of disease progression.
This Gag epitope KF11 is highly variant in the African cohort when restricted by B*5703, but is conserved in the Caucasian B*5701-positive cohort.

References

Frater2007 A. J. Frater, H. Brown, A. Oxenius, H. F. Günthard, B. Hirschel, N. Robinson, A. J. Leslie, R. Payne, H. Crawford, A. Prendergast, C. Brander, P. Kiepiela, B. D. Walker, P. J. R. Goulder, A. McLean, and R. E. Phillips. Effective T-Cell Responses Select Human Immunodeficiency Virus Mutants and Slow Disease Progression. J. Virol., 81(12):6742-6751, Jun 2007. PubMed ID: 17409157. Show all entries for this paper.

Displaying record number 61214

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, escape, HLA associated polymorphism

Notes

This review follows protective HLA-I molecules and their conserved p24 Gag epitopes that escape with a fitness cost to viral replicative capacity (VRC). Compensatory viral mutations can correct for VRC loss to different extents. This results in protective HLA losing impact as well as a modest decline in virulence of HIV with reduced VRC.
Chronic infection immunodominant epitope KF11, KAFSPEVIPMF, is restricted by strongly protective alleles. Escapes are found at A163G/S, with partial compensatory mutation S165N/K to counter VRC loss.

References

Kloverpris2015a Henrik N. Kløverpris, Alasdair Leslie, and Philip Goulder. Role of HLA Adaptation in HIV Evolution. Front. Immunol., 6:665, 18 Jan 2016. PubMed ID: 26834742. Show all entries for this paper.

Displaying record number 61197

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, TCR usage

Notes

TCR bias for pMHC is known to be structure-dependent. Three kinds of bias are described in this review (1) Type 1 where at least one biased V region is selected but no conserved CDR3 usage is seen, Type 2 (2) CDR3 loop has sequence conservation seen as motifs and (3) Type 3 that displays conserved Vα and/or Vβ usage as well as conservation in the CDR3 loop. KAFSPEVIPMF(K11)-B*5703 is of the Type 3 bias. KF8, a shorter variant, is partially cross reactive to some KF11-TCR specific T-cell clones.

References

Gras2008 Stephanie Gras, Lars Kjer-Nielsen, Scott R. Burrows, James McCluskey, and Jamie Rossjohn. T-Cell Receptor Bias and Immunity. Curr. Opin. Immunol., 20(1):119-125, Feb 2008. PubMed ID: 18207719. Show all entries for this paper.

Displaying record number 59010

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B, C
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Patient MHC/HLA	R039: A0101, A3101, B2705, B5701, Cw0202, Cw0602; R059: A0103, A6802, B3501, B5703, C0501, C0701; R014: A3001, A3301, B4201, B5703, C1701, C1801; R007: A2402, A8001, B0702, B5801, C0202, C0302; R036: A0201, A6802, B1401, B5801, C0302, C0802; N056: A0201, A0214, B1503, B1801, C0210, C0401; N087: A0301, A3001, B5703, B5801, C0602, C1801; K140: A0301, A6801, B5703, B5801, C0302, C0701; K061: A0301, A6601, B5703, B5801, C0302, C1801; 468: A0202, A6801, B5703, B5801, C0602, C0701
Country	South Africa, United Kingdom
Experimental methods	HLA binding
Keywords	epitope processing

Notes

As opposed to protective HLA-B*57 alleles (HLA-B*5701 and -B*5703), the related HLA-B*5801, differing at only 3 amino acid residues, is unable to present immunodominant Gag epitope KAFSPEVIPMF, KF11. While capable of binding KF11 at a comparable level as well as presenting it when pulsed with KF11 in vitro, HLA-B*5801+ cells do not process and subsequently present KF11. They are however, able to process and present other immunodominant Gag epitopes like TW9 and QW9.
KF11 is targeted significantly more by subjects expressing B*57 than B*58 (B*5701-subjects targeting B-clade KF11 and B*5703-subjects targeting C-clade KF11). But KF11, whether the optimal epitope itself or whether part of 18-mer WVWVIEEKAFSPEVIPMF or 15-mer EEKAFSPEVIPMF, can elicit CTL response in individuals heterozygous for HLA-B*5701 and -B*5801. Thus, in cells heterozygous for HLAs-B*5801 and -B*5701, B*5801 cannot abrogate processing, presentation of KF11 and CTL response to it.

References

Kloverpris2013b Henrik N. Kløverpris, Anette Stryhn, Mikkel Harndahl, Rebecca Payne, Greg J. Towers, Fabian Chen, Lynn Riddell, Bruce D. Walker, Thumbi Ndung'u, Alasdair Leslie, Soren Buus, and Philip Goulder. HLA-Specific Intracellular Epitope Processing Shapes an Immunodominance Pattern for HLA-B*57 That Is Distinct from HLA-B*58:01. J. Virol., 87(19):10889-10894, Oct 2013. PubMed ID: 23864640. Show all entries for this paper.

Displaying record number 58795

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B5701, B5703)
Immunogen
Experimental methods
Keywords	review

Notes

The authors review the interaction between HLA-B alleles and epitopes that are able to control viral evolution.
p24 Gag epitope KAFSPEVIPMF has residue K at position P1, binding pocket A; ATS at position P2, binding to HLA pocket B; and residue FW at the C-terminal, binding to HLA pocket F. Restricting HLA is B*5701/B*5703 [Goulder et al. ARHR 12:1691-1698 (1996)].

References

Goulder2012 Philip J. R. Goulder and Bruce D. Walker. HIV and HLA Class I: An Evolving Relationship. Immunity, 37(3):426-440, 21 Sep 2012. PubMed ID: 22999948. Show all entries for this paper.

Displaying record number 55053

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	subtype comparisons, HLA cross-presentation, variant cross-reactivity

Notes

The pattern of immunodominance and epitope clustering within Gag and Nef proteins in subtype A infected individuals was similar to that seen in subtype B and C infections. An immunodominant HLA-C restricted epitope, YVDRFFKTL (YL9 from Gag protein) was observed and restricted to Cw0304.
The sequences EKAFSPEVIPMFSAL and EKgFnPEVIPMFSAL are associated with HLA-B*5701/03 and contain the epitope KAFSPEVIPMF (KF11). Variable cross-reactivity was seen between subjects with respect to the 2 sequence variants.

References

Currier2006 Jeffrey R. Currier, Unchalee Visawapoka, Sodsai Tovanabutra, Carl J. Mason, Deborah L. Birx, Francine E. McCutchan, and Josephine H. Cox. CTL Epitope Distribution Patterns in the Gag and Nef Proteins of HIV-1 from Subtype A Infected Subjects in Kenya: Use of Multiple Peptide Sets Increases the Detectable Breadth of the CTL Response. BMC Immunol, 7:8, 2006. PubMed ID: 16620386. Show all entries for this paper.

Displaying record number 55766

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	TCR usage

Notes

To assess the role of TCR beta chain usage that is epitope-specific, 9 subjects with HLA-B*5701 or -B*5703-restricted, KF11-specific CTLs were studied. It was found that 8 subjects selectively recruited the TRBV7 chain even though it did not seem to confer any advantage.
With a large range of epitope-specific TCR clonotypes in use in the subjects, there was still no structural or functional advantage to TRBV7, except perhaps in its functional avidity for a KF11 variant, K162R, rAFSPEVIPMF.

References

Simons2008 Brenna C. Simons, Scott E. VanCompernolle, Rita M. Smith, Jie Wei, Louise Barnett, Shelly L. Lorey, Dirk Meyer-Olson, and Spyros A. Kalams. Despite Biased TRBV Gene Usage against a Dominant HLA B57-Restricted Epitope, TCR Diversity Can Provide Recognition of Circulating Epitope Variants. J. Immunol., 181(7):5137-5146, 1 Oct 2008. PubMed ID: 18802118. Show all entries for this paper.

Displaying record number 54815

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Country	Kenya, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Tetramer binding
Keywords	immunodominance, TCR usage, structure, characterizing CD8+ T cells

Notes

CD8+ T cell repertoire recognizing KAFSPEVIPMF [KF11] and variants and the structure of individual B*57-peptide complexes were studied.
In addition, immunodominancy of the previously mapped B*57 epitopes during chronic infection was assessed. KGFNPEVIPMF and ISPRTLNAW were immunodominant both in frequency and magnitude of recognition.
KAFSPEVIPMF and variant KgFnPEVIPMF induce distinct functional responses in KAFSPEVIPMF and KgFnPEVIPMF specific T cells, while the structures of B*57-peptide complexes are similar.
HLA-restriction for KAFSPEVIPMF was -B*5701 and for KgFnPEVIPMF was -B*5703.

References

Gillespie2006 Geraldine M. A. Gillespie, Guillaume Stewart-Jones, Jaya Rengasamy, Tara Beattie, Job J. Bwayo, Francis A. Plummer, Rupert Kaul, Andrew J. McMichael, Philippa Easterbrook, Tao Dong, E. Yvonne Jones, and Sarah L. Rowland-Jones. Strong TCR Conservation and Altered T Cell Cross-Reactivity Characterize a B*57-Restricted Immune Response in HIV-1 Infection. J. Immunol., 177(6):3893-3902, 15 Sep 2006. PubMed ID: 16951352. Show all entries for this paper.

Displaying record number 55092

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	B, C
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Country	India, South Africa, United Kingdom, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay, Proliferation
Keywords	subtype comparisons, escape, TCR usage, mutation acquisition

Notes

To study the contributions of HLA alleles and TCRs to the prevention of viral escape, HLAs B*5701 and B*5703 that differ at only 2 residues were followed with epitope KF11 and variants. B*5701-KF11 allowed fewer viral mutations along with a narrow TCR repertoire while B*5703-KF11 had a greater repertoire of TCR but also greater numbers of escape mutations. Therefore extensive TCR diversity is not a prerequisite to the prevention of viral mutations. More heterogeneous TCR-beta chains were also seen in the HLA-B*5703-KF11 situation and greater numbers of KF11 variants arose especially in clade C-infected subjects.
For both Clades B and C HIV-1, this epitope KAFSPEVIPMF (wt) i.e. KF11 spawned variants KgFSPEVIPMF (A2G), KnFSPEVIPMF (A2N), KsFSPEVIPMF (A2S), KsFnPEVIPMF (A2S-S4N) and KsFSPEiIPMF (A2S-V7I). In addition, Clade C also allowed variants KgFnPEVIPMF (A2G-S4(N/K)) and KgFkPEVIPMF (A2G-S4(N/K). Overall, HLA-B*5703 subjects showed more of these sequence variants than HLA-B*5701 possessing subjects did.

References

Yu2007a Xu G Yu, Mathias Lichterfeld, Senica Chetty, Katie L. Williams, Stanley K. Mui, Toshiyuki Miura, Nicole Frahm, Margaret E. Feeney, Yanhua Tang, Florencia Pereyra, Montiago X. Labute, Katja Pfafferott, Alisdair Leslie, Hayley Crawford, Rachel Allgaier, William Hildebrand, Richard Kaslow, Christian Brander, Todd M. Allen, Eric S. Rosenberg, Photini Kiepiela, Madhu Vajpayee, Paul A. Goepfert, Marcus Altfeld, Philip J. R. Goulder, and Bruce D Walker. Mutually Exclusive T-Cell Receptor Induction and Differential Susceptibility to Human Immunodeficiency Virus Type 1 Mutational Escape Associated with a Two-Amino-Acid Difference between HLA Class I Subtypes. J. Virol., 81(4):1619-1631, Feb 2007. PubMed ID: 17121793. Show all entries for this paper.

Displaying record number 59380

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	B, C
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Country	Barbados, Botswana, Spain, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Relative replication capacity assay, TCR binding
Keywords	subtype comparisons, variant cross-reactivity

Notes

Response to KF11 in B*5703-positive subtype C-infected subjects is associated with a lower viral setpoint, while response in B*5701-positive B-infected subjects is associated with a 10-fold higher viral setpoint. This difference seems to depend strongly on the residue at Gag173.
B-infected B*5701-positive KF11 responders have a higher viral setpoint than non-responders.
Escape variants A163G and S165N are selected in ˜70% of C-infected B*5703-positive subjects, but are not found in B-infected B*5703-positive subjects i.e. not associated with B*5703.

References

Payne2014 R. P. Payne, S. Branch, H Kløverpris, P. C. Matthews, C. K. Koofhethile, T. Strong, E. Adland, E. Leitman, J. Frater, T. Ndung'u, E. Hunter, R. Haubrich, B. Mothe, A. Edwards, L. Riddell, F. Chen, P. R. Harrigan, Z. L. Brumme, S. Mallal, M. John, J. P. Jooste, R. Shapiro, S. G. Deeks, B. D. Walker, C. Brander, C. Landis, J. M. Carlson, J. G. Prado, and P. J. R. Goulder. Differential Escape Patterns within the Dominant HLA-B*57:03-Restricted HIV Gag Epitope Reflect Distinct Clade-Specific Functional Constraints. J. Virol., 88(9):4668-4678, May 2014. PubMed ID: 24501417. Show all entries for this paper.

Displaying record number 52191

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KAFS
Subtype	A, B
Species (MHC/HLA)	human(B5701, B5703)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons, rate of progression

Notes

CTL responses of eight HIV+ slow progressors from Nairobi Kenya or Oxford, UK who were B*5701 or B*5703 were studied, as B*57 is associated with slow progression.
This epitope is located between the structurally conserved alpha-helix 1 and alpha-helix 2 (H1-H2) region of the p24 capsid protein, and tends to elicit strong reactions in B*57 individuals.
Broad heterogeneous cross-clade reactivity to 6 clade variants of the KAFS peptide sequence were observed in one B*5701 and 5 B*5703 HLA-restricted patients, measured by IFN-γ production Elispot assays as well as tetramer binding. The clade variants were: KAFSPEVIPMF (clades A and B), kGfNpevipmf (clades A/AC); kaLspevipmf (clade A); kafspevipVf (clade A); kafNpeIipmf (group O); kafspeIipmf (A/C); kafsQevipmf (A/C); and kaLspevipmf KNFSPEVIPMF A/G). Not all variants were well recognized in all patients, for example kafsQevipmf was not able to induce IFN gamma production in 3/6 tested, and had a diminished capacity to sensitize target cells for lysis.

References

Gillespie2002 Geraldine M. A. Gillespie, Rupert Kaul, Tao Dong, Hong-Bing Yang, Tim Rostron, Job J. Bwayo, Peter Kiama, Tim Peto, Francis A. Plummer, Andrew J. McMichael, and Sarah L. Rowland-Jones. Cross-Reactive Cytotoxic T Lymphocytes against a HIV-1 P24 Epitope in Slow Progressors with B*57. AIDS, 16(7):961-972, 3 May 2002. PubMed ID: 11953462. Show all entries for this paper.

Displaying record number 53635

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Country	Ethiopia
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, escape, variant cross-reactivity

Notes

HLA-B57 is associated with slow progression. Epitope sequence variation and CD8 T-cell responses were analyzed in HLA-B*5703-positive individuals from Ethiopia. KF11 epitope and its variants were found to be immunodominant in these subjects. Two HLA-B*5702 subjects did not respond to the KF11 epitope or its variants.
5 variants of the epitope were observed: KAFSPEVIPMF, KnFSPEVIPMF, rAFSPEVIPMF, KgFnPEVIPMF. Depending on the subject, different versions of these variants were more or less susceptible to their CD8+ T cells, i.e., one person's escape form was another person's susceptible form.
Responses against KnFSPEVIPMF were strong but subdominant in subjects carrying KAFSPEVIPMF and KnFSPEVIPMF and there was little or no response in subjects carrying KgFnPEVIPMF.
Responses against rAFSPEVIPMF were among maximal in subjects carrying KAFSPEVIPMF, KnFSPEVIPMF and rAFSPEVIPMF but there was little or no response in subjects carrying KgFnPEVIPMF.
Responses against KgFnPEVIPMF were strong but subdominant in subjects carrying KAFSPEVIPMF and KnFSPEVIPMF. In subjects carrying KgFnPEVIPMF there was a strong response against the index peptide but little or no response against other peptides. Subject carrying provirus with rAFSPEVIPMF showed dramatic nonrecognition of KgFnPEVIPMF.

References

Currier2005 Jeffrey R. Currier, Matthew E. Harris, Josephine H. Cox, Francine E. McCutchan, Deborah L. Birx, Shlomo Maayan, and Guido Ferrari. Immunodominance and Cross-Reactivity of B5703-Restricted CD8 T Lymphocytes from HIV Type 1 Subtype C-Infected Ethiopians. AIDS Res. Hum. Retroviruses, 21(3):239-245, Mar 2005. PubMed ID: 15795531. Show all entries for this paper.

Displaying record number 56590

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(161-171)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Country	South Africa, Zambia
Experimental methods
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

A cohort of clade C-infected Zambian HIV-1 transmission pairs was studied. Accumulation in the donor of HLA-B restricted mutations in Gag, but not in Nef resulted in a reduced viral load in a recipient upon transmission.
20 mutations in Gag and 11 mutations in Nef, within or flanking CTL epitopes, were considered based on data from a Clade C South African cohort. HLA-B*5703-restricted KAFSPEVIPMF (KF11) was associated with polymorphisms at K(A)FSPEVIPMF and KAF(S)PEVIPMF.

References

Goepfert2008 Paul A. Goepfert, Wendy Lumm, Paul Farmer, Philippa Matthews, Andrew Prendergast, Jonathan M. Carlson, Cynthia A. Derdeyn, Jianming Tang, Richard A. Kaslow, Anju Bansal, Karina Yusim, David Heckerman, Joseph Mulenga, Susan Allen, Philip J. R. Goulder, and Eric Hunter. Transmission of HIV-1 Gag Immune Escape Mutations Is Associated with Reduced Viral Load in Linked Recipients. J. Exp. Med., 205(5):1009-1017, 12 May 2008. PubMed ID: 18426987. Show all entries for this paper.

Displaying record number 56470

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

HLA-associated polymorphisms were studied in a cohort of 710 chronic subtype C patients from South Africa. 84 HLA Class I-associated polymorphisms were identified, 73% of them with HLA-B. The viral set points associated with HLA allele correlated with the number of reversions associated with that allele, (HLA-B in Gag, HLA-C in Pol).
KAFSPEVIPMF is a previously described HLA-B*5703-restricted epitope (part of Gag reacting peptides NAWVKVIEEKaFSPEVIPMFT and WVKVIEEKAFsPEVIPMFTAL) that contains a B*5703-associated sequence polymorphism at residue A and S (KaFSPEVIPMF/KAFsPEVIPMF).

References

Matthews2008 Philippa C. Matthews, Andrew Prendergast, Alasdair Leslie, Hayley Crawford, Rebecca Payne, Christine Rousseau, Morgane Rolland, Isobella Honeyborne, Jonathan Carlson, Carl Kadie, Christian Brander, Karen Bishop, Nonkululeko Mlotshwa, James I. Mullins, Hoosen Coovadia, Thumbi Ndung'u, Bruce D. Walker, David Heckerman, and Philip J. R. Goulder. Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point. J. Virol., 82(17):8548-8559, Sep 2008. PubMed ID: 18596105. Show all entries for this paper.

Displaying record number 57990

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Country	South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	computational epitope prediction, optimal epitope

Notes

A prediction tool, HLArestrictor, was developed to predict minimal epitopes from longer peptides. Minimal epitopes were predicted and validated for 18 EliSpot-positive 18mers.
KAFSPEVIPMF was predicted from EliSpot-positive 18mer WVKVIEEKAFSPEVIPMF. The epitope was validated in one B*5703-positive HIV-positive individual by tetramer staining.

References

Displaying record number 58423

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	A1
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	Other
Keywords	assay or method development

Notes

Ultra-deep parallel pyrosequencing using nested PCR was compared to and found to be vastly superior to Sanger clone-based sequencing. 96 ART-naive HIV-1 (clade A1, B, C or D) -infected subjects' HIV-Gag protein when sequenced by both methods, revealed 14,034 variations by pyrosequencing technology versus 3,632 variations by Sanger's method. These variations were located in previously experimentally determined CTL epitopes of Gag. The sequencing method chosen for a study affects genetic variations found, host-virus interactions detected and evolutionary conclusions drawn.
Parallel 454 pyrosequencing method detected sequence that generated a cosensus epitope read of KAFSPEVIPMF from patient ML1111. When Sanger clone-based sequencing was used however, the same functional, immunogenic site output a different consensus epitope of K(K/R)AFS(N/S)PEVIPMF.

References

Liang2011 Binhua Liang, Ma Luo, Joel Scott-Herridge, Christina Semeniuk, Mark Mendoza, Rupert Capina, Brent Sheardown, Hezhao Ji, Joshua Kimani, Blake T. Ball, Gary Van Domselaar, Morag Graham, Shane Tyler, Steven J. M. Jones, and Francis A. Plummer. A Comparison of Parallel Pyrosequencing and Sanger Clone-Based Sequencing and Its Impact on the Characterization of the Genetic Diversity of HIV-1. PLoS One, 6(10):e26745, 2011. PubMed ID: 22039546. Show all entries for this paper.

Displaying record number 58684

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
		Show epitope variants
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	HLA associated polymorphism

Notes

1,010-HIV C clade-chronically infected subjects were tested in order to distinguish levels of immune control by related but different HLA-B*57/58. B*57 micropolymorphisms (B*5703 and B*5702) as well as B*5801 have differing CTL specificity and also present different p24 Gag epitopes. This results in different immune selection pressures on the HIV-C virus.
Though all three studied HLA alleles, B*5801, B*5702 and B*5703 are significantly associated with lower viral-load (VL) set points, HLA-B*5703, followed closely by B*5702 is the most potent controller with lowest VL and HLA-B*5702, followed by B*5703 and then B*5801 are associated with highest CD4 counts.
By using 410 overlapping 18-mers that span the HIV-C proteome in EliSpot assays, 17 epitopes were identified that are presented by one of HLAs-B*5801/5702/5703, 13 of them novel.
Immunodominant epitope KF11, KAFSPEVIPMF, was previously known to be restricted by HLA-B*5703. KF11 was targeted by 76% subjects expressing B*5703, 10% expressing B*5801 and none of those expressing B*5702.
The binding affinity and HLA-peptide stability of KF11 to each HLA follows the same pattern as its restriction i.e. highest affinity and stability are seen with B*5703, much less with B*5801 and least with B*5702.
There were no escapes detected in HLA-B*5801 or -B*5702 positive subjects as these HLA do not recognize KF11. Escapes were detected in B*5703 subjects though.

References

Kloverpris2012 Henrik N. Kloverpris, Anette Stryhn, Mikkel Harndahl, Mary van der Stok, Rebecca P. Payne, Philippa C. Matthews, Fabian Chen, Lynn Riddell, Bruce D. Walker, Thumbi Ndung'u, Søren Buus, and Philip Goulder. HLA-B*57 Micropolymorphism Shapes HLA Allele-Specific Epitope Immunogenicity, Selection Pressure, and HIV Immune Control. J. Virol., 86(2):919-929, Jan 2012. PubMed ID: 22090105. Show all entries for this paper.

Displaying record number 53921

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
Mutational patterns in the A2 and S4 residues of KAFSPEVIPMF are associated with the presence of the HLA presenting molecule in the host.

References

Kiepiela2007 Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Isobella Honeyborne, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Khan, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, Noel McCarthy, Christian Brander, Gerald H. Learn, David Nickle, Christine Rousseau, Hoosen Coovadia, James I. Mullins, David Heckerman, Bruce D. Walker, and Philip Goulder. CD8+ T-Cell Responses to Different HIV Proteins Have Discordant Associations with Viral Load. Nat. Med., 13(1):46-53, Jan 2007. PubMed ID: 17173051. Show all entries for this paper.

Displaying record number 57440

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KAF-11
Species (MHC/HLA)	human(B*5703)
Immunogen	peptide-HLA interaction
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	structure

Notes

High resolution crystal structure analyses were performed to define interactions between long term non-progression (LTNP) HLA, B*57, and HIV-1 epitopes of differing lengths, sequence, anchorage. HLA-B*5703 was crystallized with one of 3 epitopes from Gag. Peptide conformations and MHC side chain residue roles were determined, in particular anchors at positions 2 and C terminus. Bioinformatic analysis was used to highlight HLA-B alleles that might share such binding specificities and thus be involved in LNTP.
This immunodominant epitope, KAFSPEVIPMF, of crystal structure resolution 1.6A, has alanine as its B-pocket anchor residue 2. Phenylalanine is its C-terminus anchor in the MHC F pocket. It has a large hairpin protrusion and the bulge is stabilized by prolines at positions 5, 9. KAF-11 is more stable within the HLA-B*5703 groove than KAF-8 is, consistent with its greater number of van der Waal's contacts.
Known as an HLA-B*5701-restricted epitope, KAF-11 was found to elicit CTL response in 12 of 12 HLA-B*5703+ HIV-infected, therapy-naive Kenyan women. Mean response frequency was 2120 [ranging 115-5140] SFU/million PBMC.

References

Stewart-Jones2005 Guillaume B. E. Stewart-Jones, Geraldine Gillespie, Ian M. Overton, Rupert Kaul, Philippe Roche, Andrew J. McMichael, Sarah Rowland-Jones, and E. Yvonne Jones. Structures of Three HIV-1 HLA-B*5703-Peptide Complexes and Identification of Related HLAs Potentially Associated with Long-Term Nonprogression. J. Immunol., 175(4):2459-2468, 15 Aug 2005. PubMed ID: 16081817. Show all entries for this paper.

Displaying record number 1976

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(20-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	Gag-KF11; p24-KF11
Subtype	B
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Patient MHC/HLA	00RCH59: A3402, A7401, B0801, B5703, Cw0302, Cw0701
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	HAART, ART

Notes

This study monitored epitope responses in HIV-1 infected minority women living in the United States.
24 epitopes were described -- 8 were novel, 8 used new restricting elements but were previously defined epitopes, and 8 were previously described.
Serial peptide truncations were used to define optimal epitopes for CTL cell lines isolated from 12 individuals, assayed by a Cr-release.
Subject 00RCH59 was African American, on HAART, viral load 170, CD4 count 477.
Among HIV+ individuals who carried HLA-B*57, 6/6 (100%) recognized this previously described epitope.

References

Sabbaj2003 Steffanie Sabbaj, Anju Bansal, G. Douglas Ritter, Christopher Perkins, Bradley H. Edwards, Ethan Gough, Jianming Tang, James J. Szinger, Bette Korber, Craig M. Wilson, Richard A. Kaslow, Mark J. Mulligan, and Paul A. Goepfert. Cross-Reactive CD8+ T Cell Epitopes Identified in US Adolescent Minorities. J. Acquir. Immune Defic. Syndr., 33(4):426-438, 1 Aug 2003. PubMed ID: 12869831. Show all entries for this paper.

Displaying record number 165

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(162-172 LAI)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes this is a B*5703 epitope.

References

Displaying record number 62165

HXB2 Location	Gag(162-172) p24(30-40)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	Gag-KF11
Species (MHC/HLA)	human(B*5703)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review, escape, HLA associated polymorphism

Notes

This review focuses on HLA associated polymorphisms and how studying HIV adaptation in the context of HLA can show us epitopes that are well conserved with high mutational barriers to escape as well as epitopes that are extensively mutated in circulation within some populations and viral subtypes.
1/3rd of HLA-associated polymorphisms at position 161, which is one residue upstream of KF11, KAFSPEVIPMF, are differentially selected between subtypes A1 and D. These subtypes cocirculate in East Africa. [Kinloch et al. JVI 93(1):1-24 (2019)]

References

Avila-Rios2019 Santiago Avila-Rios, Jonathan M. Carlson, Mina John, Simon Mallal, and Zabrina L. Brumme. Clinical and Evolutionary Consequences of HIV Adaptation to HLA: Implications for Vaccine and Cure. Curr. Opin. HIV AIDS, 14(3):194-204, May 2019. PubMed ID: 30925534. Show all entries for this paper.

Displaying record number 55863

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	A, B
Species (MHC/HLA)	human(B58)
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	subtype comparisons

Notes

By studying Gag p24 in different subtypes of subjects, previously discovered and new epitopes were identified. New T cell epitopes, both CD8 and CD4, related to the patients' HLA are described.
T cells cross-reacted to peptides from different patient subtypes, and this cross-reactivity was distributed along the entire p24 protein.
HLA-B58-restricted epitope KAFSPEVIPMF is from subtype A and B libraries, and is reactive as part of peptide EKAFSPEVIPMFSAL in a subtype B-carrying subject.

References

Gudmundsdotter2008 L. Gudmundsdotter, D. Bernasconi, B. Hejdeman, E. Sandstrom, A. Alaeus, K. Lidman, B. Ensoli, B. Wahren, and S. Buttò. Cross-Clade Immune Responses to Gag p24 in Patients Infected with Different HIV-1 Subtypes and Correlation with HLA Class I and II Alleles. Vaccine, 26(40):5182-5187, 19 Sep 2008. PubMed ID: 18479789. Show all entries for this paper.

Displaying record number 1462

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24(30-40)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B58)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

One of the 51 HIV-1 epitopes selected by Ferrari et al. as good candidate CTL epitopes for vaccines by virtue of being conserved and presented by common HLA alleles.

References

Ferrari2000 G. Ferrari, D. D. Kostyu, J. Cox, D. V. Dawson, J. Flores, K. J. Weinhold, and S. Osmanov. Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines. AIDS Res. Hum. Retroviruses, 16(14):1433-43, 20 Sep 2000. PubMed ID: 11018863. Show all entries for this paper.

Displaying record number 53704

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Subtype	B, G
Species (MHC/HLA)	human(B58)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A36, B45, B58, Cw3, Cw6
Country	Nigeria
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons

Notes

Cross-clade CTL responses in 10 non-B HIV-1 infected individuals were evaluated. T-cell reactivity was tested against peptide pools of clade B Gag, Pol, Nef, Rev and Tat. Nine individuals demonstrated cross-reactive T-cell responses to clade A, B, and C Gag pools; 6/7 patients that responded to Nef-B also reacted to clade A and C Nef pools. An inverse correlation was observed between the sequence divergence of the HLA class I restricted epitopes and the height of the T-cell responses, which in Gag could be explained through variations in the HLA-anchor residues. 42% of the responses were directed to regions containing new epitopes.
This previously described epitope was embedded in a B clade peptide that was recognized by T-cells from an infected person carrying subtype G Gag. The autologous epitope sequence in this person matched the known epitope.

References

Geels2005 Mark J. Geels, Sheri A. Dubey, Kiersten Anderson, Elly Baan, Margreet Bakker, Georgios Pollakis, William A. Paxton, John W. Shiver, and Jaap Goudsmit. Broad Cross-Clade T-Cell Responses to Gag in Individuals Infected with Human Immunodeficiency Virus Type 1 Non-B Clades (A to G): Importance of HLA Anchor Residue Conservation. J. Virol., 79(17):11247-11258, Sep 2005. PubMed ID: 16103177. Show all entries for this paper.

Displaying record number 57885

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human(B*5801)
Immunogen	HIV-1 infection
Patient MHC/HLA	A0205, A2601, B0705, B5801, Cw0701, Cw0702
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, acute/early infection

Notes

HLA-B*5801 is associated with slow progression. Six B*5801-positive subtype C-infected subjects were followed for up to 31 months from infection. CTL responses during acute infection predominantly targeted the TW10 and KF9 epitopes. Transmitted escape and compensatory mutations appeared to limit the protective effect of the B*5801 allele.
In EliSpot assays of overlapping peptides across the entire proteome, 1/6 patients targeted a peptide containing this epitope, KAFSPEVIPMF; a single-peptide response was not confirmed. Subject CAP268 with the best control of viral replication displayed CTL responses to both this epitope, KF11, and TW10.

References

Chopera2011 D. R. Chopera, M. Mlotshwa, Z. Woodman, K. Mlisana, D. de Assis Rosa, D. P. Martin, S. Abdool Karim, C. M. Gray, C. Williamson, and CAPRISA 002 Study Team. Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals. J. Virol., 85(14):7070-7080, Jul 2011. PubMed ID: 21613398. Show all entries for this paper.

Displaying record number 54137

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human(B*63)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes that this is an B*63 epitope.

References

Displaying record number 59887

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(C*01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
KAFSPEVIPMF had a significantly positive association with HLA C*01; it was recognized by 4/25 C*01-positive subjects and 9/201 C*01-negative subjects.

References

Displaying record number 59886

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Species (MHC/HLA)	human(C*14)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
KAFSPEVIPMF had a significantly positive association with HLA C*14; it was recognized by 5/11 C*14-positive subjects and 13/226 C*14-negative subjects.

References

Displaying record number 56734

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag(162-172 NL4-3)
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	South Africa, Zambia
Experimental methods	Other
Keywords	escape

Notes

HIV replication and disease progression were studied in two HLA-B*5703-predominant HIV-1 Clade-C-infected cohorts. Gag epitope mutations in Clade C virus appeared in the following order - ISPRTLNAW (ISW9), TSTLQEQIAW (TW10) and then KAFSPEVIPMF (KF11). Viral advantage by these escapes, especially from the KF11 CTL response, far exceeds replication fitness costs. Transmission of associated mutations to both HLA-matched and HLA-mismatched subjects resulted in rapid progression of disease. Virus in HLA-mismatched recipients speedily reverted to fitter phenotypes.
Gag epitope KF11, KAFSPEVIPMF, was found to mutate to KnFSPEVIPMF and KgFnPEVIPMF. The A163N mutant was the transmitted phenotype to recipients.

References

Crawford2009 Hayley Crawford, Wendy Lumm, Alasdair Leslie, Malinda Schaefer, Debrah Boeras, Julia G. Prado, Jianming Tang, Paul Farmer, Thumbi Ndung'u, Shabir Lakhi, Jill Gilmour, Paul Goepfert, Bruce D. Walker, Richard Kaslow, Joseph Mulenga, Susan Allen, Philip J. R. Goulder, and Eric Hunter. Evolution of HLA-B*5703 HIV-1 Escape Mutations in HLA-B*5703-Positive Individuals and Their Transmission Recipients. J. Exp. Med., 206(4):909-921, 13 Apr 2009. PubMed ID: 19307327. Show all entries for this paper.

Displaying record number 57733

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	assay or method development, characterizing CD8+ T cells

Notes

Levels of CD38, a positive marker of immunity and PD-1, a negative immune signal were studied for association with progression or control of AIDS in chronic, untreated patients. An increase in CD38/PD-1 co-expression on CTL was found in progressors. After initiation of HAART, CD38/PD-1 levels dropped. VL increase was accompanied or preceded by significant increases in CD38/PD-1 co-expression. Therefore this is the first demonstration that a highly significant difference exists between the expression of CD38/PD-1 in controllers and progressors during chronic infection.
In addition, instead of the usual use of tetrameric complexes to detect CTL response along with CD38 and PD-1 expression, Peptide stimulation and IFN-γ were used along with surface marker staining.
Epitope KAFSPEVIPMF elicited a CTL response.

References

Vollbrecht2010 Thomas Vollbrecht, Heike Brackmann, Nadja Henrich, Joerg Roeling, Ulrich Seybold, Johannes R. Bogner, Frank D. Goebel, and Rika Draenert. Impact of Changes in Antigen Level on CD38/PD-1 Co-Expression on HIV-Specific CD8 T Cells in Chronic, Untreated HIV-1 Infection. J. Med. Virol., 82(3):358-370, Mar 2010. PubMed ID: 20087935. Show all entries for this paper.

Displaying record number 61342

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	Gag
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	vaccine
Country	Australia, Brazil, Canada, Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico, United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses, assay or method development, optimal epitope

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5)
Vaccine component	Gag, Nef, Pol

Notes

Small pools of 15-mer peptides (7-30) were used to map T-cell epitopes. 2 such methods (mini- and maxi-pool strategies) used up to 7.7x less EliSpot assays than the traditional 'test-all' method of using each peptide-epitope individually. While the test-all method identified the largest number of epitopes and some EliSpots are only positive when shorter, more optimal peptides are used, overall this strategy is best for following vaccine trials and other large epitope-mapping studies.
37 15-mers and 27 optimal peptides representing 13 optimal epitopes gave CTL responses out of the 134 tested.
Optimal epitope KAFSPEVIPMF elicited response of 48.5 sfc/million PBMC from participants in the Step HIV-1 vaccine efficacy trial who were uninfected at the time of testing.

References

Fiore-Gartland2016 Andrew Fiore-Gartland, Bryce A. Manso, David P. Friedrich, Erin E. Gabriel, Greg Finak, Zoe Moodie, Tomer Hertz, Stephen C. De Rosa, Nicole Frahm, Peter B. Gilbert, and M Juliana McElrath. Pooled-Peptide Epitope Mapping Strategies Are Efficient and Highly Sensitive: An Evaluation of Methods for Identifying Human T Cell Epitope Specificities in Large-Scale HIV Vaccine Efficacy Trials. PLoS One, 11(2):e0147812, 2016. PubMed ID: 26863315. Show all entries for this paper.

Displaying record number 61640

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Epitope Name	KF11
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Canada
Experimental methods	Chromium-release assay, Other
Keywords	epitope processing, escape

Notes

HIV-1 escape by an antigen processing mutation was identified and found to show no change in epitope presentation and thus recognition. Epitope KAFSPEVIPMF showed enhanced presentation when flanked by cleavable motifs LL and FF, but not by motifs II, VV, DD, HH or SS.

References

Zhang2012 Shao Chong Zhang, Eric Martin, Mariko Shimada, Sasha Blue Godfrey, Jennifer Fricke, Shirley Locastro, Nicole Y. Lai, Paul Liebesny, Jonathan M. Carlson, Chanson J. Brumme, Oluwatobi Awele Ogbechie, Huabiao Chen, Bruce D. Walker, Zabrina L. Brumme, Daniel G. Kavanagh, and Sylvie Le Gall. Aminopeptidase Substrate Preference Affects HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-Infected Individuals. J. Immunol., 188(12):5924-5934, 15 Jun 2012. PubMed ID: 22586036. Show all entries for this paper.

Displaying record number 1336

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location	p24
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

This study examines CTL responses in HIV exposed, persistently seronegative individuals, HEPS, who eventually seroconverted -- 11/114 HEPS Nairobi sex workers eventually seroconverted, and for six of these HIV CTL reactive epitopes had been defined while seronegative.
The epidemiological factor associated with seroconversion was stopping sex work. HIV-specific CTL activity declined when HEPS sex workers stopped working for a period or retired.
This epitope was recognized by 1/22 HEPS sex worker controls, ML1250.

References

Kaul2001 R. Kaul, S. L. Rowland-Jones, J. Kimani, T. Dong, H. B. Yang, P. Kiama, T. Rostron, E. Njagi, J. J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. Late Seroconversion in HIV-Resistant Nairobi Prostitutes Despite Pre-Existing HIV-Specific CD8+ Responses. J. Clin. Invest., 107(3):341-349, Feb 2001. URL: http://www.jci.org/cgi/content/full/107/3/341. PubMed ID: 11160158. Show all entries for this paper.

Displaying record number 55100

HXB2 Location	Gag(162-172) p24(30-40) DNA(1273..1305)	Gag Epitope Map
Author Location
Epitope	`KAFSPEVIPMF`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	binding affinity, acute/early infection

Notes

Differences in early versus chronic AIDS include a decline in CTL number accompanied by a reducing viremia. Comparative analysis of such CTLs in this study show that early infection is characterized by a different clonotypic composition and higher functional avidity of CTLs followed by their selective depletion during transition to chronic disease. The total magnitude of CTL cytokine production is lower in early infection. Intraindividual, early CTLs' functional avidity for the same epitope decreases concomitantly with a reduction in clonotypic TCR repertoire especially of strongly activated and CD127lo, CD38+, Ki-67hi CTLs while progressing to chronic infection states.
None of the target epitopes, including this epitope KAFSPEVIPMF seen in 1 patient, underwent sequence changes.

References

Lichterfeld2007 Mathias Lichterfeld, Xu G. Yu, Stanley K. Mui, Katie L. Williams, Alicja Trocha, Mark A. Brockman, Rachel L. Allgaier, Michael T. Waring, Tomohiko Koibuchi, Mary N. Johnston, Daniel Cohen, Todd M. Allen, Eric S. Rosenberg, Bruce D. Walker, and Marcus Altfeld. Selective Depletion of High-Avidity Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T Cells after Early HIV-1 Infection. J. Virol., 81(8):4199-4214, Apr 2007. PubMed ID: 17287271. Show all entries for this paper.