Search CTL/CD8+ T-Cell Epitope Database

Found 25 matching records:

Displaying record number 54565

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Intracellular cytokine staining, Other
Keywords	rate of progression, escape, mutation acquisition

Notes

To correlate evolving HIV-1 populations with HLA-A2 restricted immune responses for epitopes in Gag, Pol, Env and Nef, 11 treatment-naive subjects were longitudinally studied. Results show that increased viral load is often associated with broad CTL responses early in infection that persist as an "immunological footprint". Conversely, early, restricted responses may help limit viral load. Phylogenetic and functional evidence of viral escape is seen in Gag, Nef and Pol. Gag and Nef show flanking epitope changes restricted by non-HLA-A2 alleles. As far as modes of viral adaptation, CTL responses were seen to develop both against static viral populations resulting in viral evolution to HLA-A2 as well as against existing mutants resulting in reselection of consensus B-like variants. This study reinforces that CTL immune responses detected are not necessarily beneficial to patients, but may be "footprints" from early effective responses that the virus has since escaped.

References

Karlsson2007 Annika C. Karlsson, Astrid K. N. Iversen, Joan M. Chapman, Tulio de Oliviera, Gerald Spotts, Andrew J. McMichael, Miles P. Davenport, Frederick M. Hecht, and Douglas F. Nixon. Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape. PLoS ONE, 2:e225, 2007. PubMed ID: 17311088. Show all entries for this paper.

Displaying record number 56190

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(221-)
Epitope	`LTFGWCFKL`	Epitope Alignment
Species (MHC/HLA)	human(A*0201)
Immunogen	vaccine
Country	Botswana, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine strain	multiple epitope immunogen

Notes

This is a trial of a multi-epitope DNA vaccine that included 21 CTL epitopes, which are conserved among clades A,B,C,D and CRFs and are supertype binding peptides of A1, A3 and B7 supertypes. Participants were from US and Botswana.
The vaccine was safe and well-tolerated, but the rate of CTL induction was low. CD8+ responses (and no CD4+ responses) were detected in 3/26 subjects using chromium release assay and in 2/42 subjects using IFN-γ ELISPOT assay.
This epitope was included in the vaccine.

References

Gorse2008a Geoffrey J. Gorse, Lindsey R. Baden, Margaret Wecker, Mark J. Newman, Guido Ferrari, Kent J. Weinhold, Brian D. Livingston, Tonya L. Villafana, Hongli Li, Elizabeth Noonan, Nina D. Russell, and HIV Vaccine Trials Network. Safety and Immunogenicity of Cytotoxic T-Lymphocyte Poly-Epitope, DNA Plasmid (EP HIV-1090) Vaccine in Healthy, Human Immunodeficiency Virus Type 1 (HIV-1)-Uninfected Adults. Vaccine, 26(2):215-223, 10 Jan 2008. PubMed ID: 18055072. Show all entries for this paper.

Displaying record number 54322

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Species (MHC/HLA)	human(A*0201)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Cytokine production, HLA binding, Other
Keywords	vaccine-induced immune responses, HLA cross-presentation, HLA associated polymorphism

Notes

25 CTL epitopes with sequence conservation were studied. Population protection coverage (PPC) for 5 different ethnic groups in the US was estimated by combining HLA binding predictions and known HLA frequencies. HIV-1-naive individuals mounted a better response to the epitope pools than HIV-1 infected individuals.
A more detailed evaluation of HIV-naive T-cell responses was undertaken, limiting the study to only those peptides that are restricted to A*0201. Though the peptides could cross-recognize and bind different HLA, they were able to specifically lyse only cells of the same (A*0201) HLA-restriction. Thus, the CTL response was less degenerate than peptide binding to MHC.
In addition to the published restriction above, epitope LTFGWCFKL was predicted to be restricted by HLA A*0201.

References

Reche2006 Pedro A. Reche, Derin B. Keskin, Rebecca E. Hussey, Petronela Ancuta, Dana Gabuzda, and Ellis L. Reinherz. Elicitation from Virus-Naive Individuals of Cytotoxic T Lymphocytes Directed against Conserved HIV-1 Epitopes. Med. Immunol., 5:1, 2006. PubMed ID: 16674822. Show all entries for this paper.

Displaying record number 57106

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145 DU422)
Epitope	`LTFGWCFKL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*0201)
Immunogen	in vitro stimulation or selection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Tetramer binding
Keywords	dendritic cells

Notes

Three types of myeloid dendritic cells - monocytic dendritic cells, Langerhans cells, and interstitial dermal-intestinal dendritic cells - were shown to be able to prime CD8+ T-cell responses to HIV-1. Primed monocytic dendritic cells from 2 uninfected adult donors had broad primary T-cell reactivity, reacting with 15mers containing 42 known epitopes in Gag, Env, and Nef.
One of the reactive 15mers contained optimal epitope LTFGWCFKL, which was restricted by HLA A*0201.

References

Colleton2009 Bonnie A. Colleton, Xiao-Li Huang, Nada M. Melhem, Zheng Fan, Luann Borowski, Giovanna Rappocciolo, and Charles R. Rinaldo. Primary Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses Induced by Myeloid Dendritic Cells. J. Virol., 83(12):6288-6299, Jun 2009. PubMed ID: 19357176. Show all entries for this paper.

Displaying record number 1398

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(139-147 HXB3)
Epitope	`LTFGWCFKL`	Epitope Alignment
Species (MHC/HLA)	mouse(A*0201)
Immunogen	vaccine
Experimental methods
Keywords	binding affinity, computational epitope prediction

Vaccine Details

Vaccine type	DNA, peptide
Vaccine strain	B clade HXB3
Vaccine component	Nef
Adjuvant	Complete Freund's Adjuvant (CFA)

Notes

Ten Nef 9-mer peptides were predicted to have a strong binding affinity with HLA-A*0201 -- of these, four did bind strongly by a T2 class I stabilization assay, several others bound weakly.
A CTL immune response to only 3/10 peptides was detected by a 51Cr-release assay after immunization of HLA-A201 transgenic mice with either nef DNA under the control of a CMV promotor, coated on gold particles delivered to abdominal skin by gene gun -- LTFGWCFKL did not elicit a CTL response.
LTFGWCFKL was also tested by subcutaneous injection of Nef peptides in Freund's adjuvant, because it bound strongly to HLA-A*0201, and the peptide vaccination did elicit a response.
The lack of response to the nef DNA vaccine and the response to the peptide suggests LTFGWCFKL may not be processed.

References

Sandberg2000 J. K. Sandberg, A. C. Leandersson, C. Devito, B. Kohleisen, V. Erfle, A. Achour, M. Levi, S. Schwartz, K. Karre, B. Wahren, and J. Hinkula. Human immunodeficiency virus type 1 Nef epitopes recognized in HLA-A2 transgenic mice in response to DNA and peptide immunization. Virology, 273(1):112-9, 20 Jul 2000. PubMed ID: 10891413. Show all entries for this paper.

Displaying record number 56531

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	Nef221
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	vaccine
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine component	Other

Notes

DNA vaccine EP HIV-1090 evaluation in patients receiving ART was done. This vaccine is composed of multiple CTL epitopes, all associated with certain HLA supertypes. Differences of CTL response rate in vaccine and placebo recipients however, was not significant.
LTFGWCFKL is a Nef epitope encoded in the EP HIV-1090 polyepitope vaccine.

References

Wilson2008 Cara C. Wilson, Mark J. Newman, Brian D. Livingston, Samantha MaWhinney, Jeri E. Forster, Jim Scott, Robert T. Schooley, and Constance A. Benson. Clinical Phase 1 Testing of the Safety and Immunogenicity of an Epitope-Based DNA Vaccine in Human Immunodeficiency Virus Type 1-Infected Subjects Receiving Highly Active Antiretroviral Therapy. Clin. Vaccine Immunol., 15(6):986-994, Jun 2008. PubMed ID: 18400976. Show all entries for this paper.

Displaying record number 52694

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	Nef137
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	binding affinity, subtype comparisons, computational epitope prediction

Notes

HLA-A2-restricted HIV-1 CTL epitopes were computationally predicted. Binding affinities for HLA-A*0204, immunogenicity in HLA-A*0201 transgenic mice, and responses to the peptides in 17 HIV-1 infected patients were tested. 31 novel conserved A2 epitopes were detected. An average of 4 epitopes were recognized per patient.
This epitope was one of the previously identified HLA-A2 epitopes studied.
3/17 HIV-infected HLA-A2+ people recognized this epitope.

References

Corbet2003 Sylvie Corbet, Henrik Vedel Nielsen, Lasse Vinner, Sanne Lauemoller, Dominic Therrien, Sheila Tang, Gitte Kronborg, Lars Mathiesen, Paul Chaplin, Søren Brunak, Søren Buus, and Anders Fomsgaard. Optimization and Immune Recognition of Multiple Novel Conserved HLA-A2, Human Immunodeficiency Virus Type 1-Specific CTL Epitopes. J. Gen. Virol., 84(Pt 9):2409-2421, Sep 2003. PubMed ID: 12917462. Show all entries for this paper.

Displaying record number 53177

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	Nef137-145
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	responses in children, immunodominance, characterizing CD8+ T cells

Notes

Responses to five HLA-A2 presented epitopes in Nef were characterized in a population of 19 HIV infected adults and 21 children. The CD8 T-cell response to Nef was stronger and broader in adults than children, averaging 652 and 87 SFCs/10⁶ PBMC, and 2.6 and 0.9 recognized epitopes per person, respectively.
This epitope was second in an immunodominance hierarchy of the five A02 Nef epitopes studied.

References

Chandwani2004 R. Chandwani, K. A. Jordan, B. L. Shacklett, E. Papasavvas, L. J. Montaner, M. G. Rosenberg, D. F. Nixon, and J. K. Sandberg. Limited Magnitude and Breadth in the HLA-A2-Restricted CD8 T-Cell Response to Nef in Children with Vertically Acquired HIV-1 Infection. Scand. J. Immunol., 59(1):109-114, Jan 2004. PubMed ID: 14723629. Show all entries for this paper.

Displaying record number 56239

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location
Epitope	`LTFGWCFKL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	rate of progression, immunodominance

Notes

47 HIV-1 subtype C infected patients were followed longitudinally to determine whether there was a relation between magnitude and breadth of CTL responses in primary, acute infection (measured by IFN-gamma ELISpot) and disease progression (measured as viral load at 12 months). CTL responses to Nef were dominant (targeting 6 epitopic regions), followed by responses to Gag, Pol, Rev, Vpr, Env, Vpu, Vif and finally Tat.
LTFGWCFKL is a known HLA-A2-restricted epitope that is part of peptide PGPGVRYPLTFGWCFKLVP which elicited the most dominant response in 8/10 patients.

References

Gray2009 Clive M. Gray, Mandla Mlotshwa, Catherine Riou, Tiyani Mathebula, Debra de Assis Rosa, Tumelo Mashishi, Cathal Seoighe, Nobubelo Ngandu, Francois van Loggerenberg, Lynn Morris, Koleka Mlisana, Carolyn Williamson, Salim Abdool Karim, and CAPRISA 002 Acute Infection Study Team. Human Immunodeficiency Virus-Specific gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point. J. Virol., 83(1):470-478, Jan 2009. PubMed ID: 18945774. Show all entries for this paper.

Displaying record number 59997

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Species (MHC/HLA)	human(A*23)
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.
LTFGWCFKL had a significantly positive association with HLA A*23; it was recognized by 5/22 A*23-positive subjects and 11/289 A*23-negative subjects.

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 59998

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Species (MHC/HLA)	human(A*25)
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.
LTFGWCFKL had a significantly positive association with HLA A*25; it was recognized by 2/16 A*25-positive subjects and 0/231 A*25-negative subjects.

References

Displaying record number 1590

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(158-166)
Epitope	`LTFGWCFKL`	Epitope Alignment
Species (MHC/HLA)	human(A2 supertype)
Immunogen	HIV-1 infection
Experimental methods
Keywords	supertype, rate of progression

Notes

Long-term nonprogressors (LTNPs) had strong memory resting CD8+ T-cell responses against the majority of epitopes tested, (18 for the A2 supertype, 16 for the A3 supertype) while the effector cells of long-term nonprogressors recognized far fewer epitopes.
Progressors had memory resting CD8+ T-cells that recognized far fewer epitopes than LTNPs.
A positive correlation between effector CD8+ T-cells and plasma viremia and a negative correlation between CD8+ effector T-cells and CD4+ T-cells was observed, which may contribute to the inability of LTNPs to clear virus.
This epitope can bind all five HLA-A2 supertypes alleles (A*0201, A*0202, A*0203, A*0206 and A*6802)

References

Propato2001 A. Propato, E. Schiaffella, E. Vicenzi, V. Francavilla, L. Baloni, M. Paroli, L. Finocchi, N. Tanigaki, S. Ghezzi, R. Ferrara, R. Chesnut, B. Livingston, A. Sette, R. Paganelli, F. Aiuti, G. Poli, and V. Barnaba. Spreading of HIV-specific CD8+ T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity. Hum. Immunol., 62(6):561-76, Jun 2001. PubMed ID: 11390031. Show all entries for this paper.

Displaying record number 56507

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	Nef221
Subtype	A, B, C
Species (MHC/HLA)	human, mouse(A2 supertype)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	binding affinity, supertype, vaccine-induced immune responses, HLA cross-presentation

Notes

21 supertype-A2, -A3 and -B7-restricted epitopes predicted to be immunogenic by HLA-peptide binding motifs and phenotypic frequency in individuals were recognized by HIV-1+ subjects in ELISpot assays and shown to bind with high affinity to minimum 3 HLA-alleles of the restricting supertype. These epitopes were included in DNA vaccine EP HIV-1090 that avoided immunodominant responses and did not restrict subject immunity to predicted HLA-type when tested in mice. Transgenic mice mounted a vaccine-response similar to that induced by ELISpot assay in humans.
Epitope LTFGWCFKL of the HLA-A2 supertype bound most strongly to HLA-A*6802, -A*0202, -A*0201 and -A*0206, but also to -A*0203. It was conserved 75% in subtype A, 74% in B, 100% in C and 0% in subtype D. 5/22 HLA-A2 supertype expressing HIV-1+ subjects mounted a positive ELISpot response to Nef221.

References

Wilson2003 Cara C. Wilson, Denise McKinney, Michelle Anders, Samantha MaWhinney, Jeri Forster, Claire Crimi, Scott Southwood, Alessandro Sette, Robert Chesnut, Mark J Newman, and Brian D Livingston. Development of a DNA Vaccine Designed to Induce Cytotoxic T Lymphocyte Responses to Multiple Conserved Epitopes in HIV-1. J. Immunol., 171(10):5611-5623, 15 Nov 2003. PubMed ID: 14607970. Show all entries for this paper.

Displaying record number 59995

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Species (MHC/HLA)	human(A*32)
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.
LTFGWCFKL had a significantly positive association with HLA A*32; it was recognized by 10/30 A*32-positive subjects and 16/311 A*32-negative subjects.

References

Displaying record number 59996

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Species (MHC/HLA)	human(A*6802)
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.
LTFGWCFKL had a significantly positive association with HLA A*6802; it was recognized by 5/26 A*6802-positive subjects and 6/263 A*6802-negative subjects.

References

Displaying record number 60001

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Species (MHC/HLA)	human(A*80)
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.
LTFGWCFKL had a significantly positive association with HLA A*80; it was recognized by 1/1 A*80-positive subjects and 5/262 A*80-negative subjects.

References

Displaying record number 53667

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Subtype	B, C
Species (MHC/HLA)	human(B*1517, B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	A36, A66, B1517, B53, Cw04, Cw06; A02, A23, B35, B57, Cw04, Cw07
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	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.
Optimal epitope was defined in 2 people, 1 carrying HLA-B*1517(B63), the other carrying B57.

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 60000

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Species (MHC/HLA)	human(B*1540)
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.
LTFGWCFKL had a significantly positive association with HLA B*1540; it was recognized by 1/1 B*1540-positive subjects and 4/261 B*1540-negative subjects.

References

Displaying record number 54132

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location
Epitope	`LTFGWCFKL`	Epitope Alignment
Species (MHC/HLA)	human(B*57)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes that this is an B*57 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 59301

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression

Notes

620 patients in early/acute stages of infection were screened for Elispot responses to optimally defined epitopes to find associations between specific CTL responses and long-term control of HIV-1. Seven epitope-specific responses were associated with delayed initiation of ART, and 12 were associated with a more rapid initiation of therapy. While initial viremia, HLA Class I genotype and viral set points were associated, breadth and magnitude of response did not influence early viral set point. A broader CTL response to Gag, however, associates with slower disease progression.
Initial specificity of CTL response rather than restricting HLA-I molecule contributes to disease control.
The HLA-B*57-restricted epitope LTFGWCFKL was associated with accelerated initiation of ART.

References

Streeck2014 Hendrik Streeck, Richard Lu, Noor Beckwith, Mark Milazzo, Michelle Liu, Jean-Pierre Routy, Susan Little, Heiko Jessen, Anthony D. Kelleher, Frederick Hecht, Rafick-Pierre Sekaly, Galit Alter, David Heckerman, Mary Carrington, Eric S. Rosenberg, and Marcus Altfeld. Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary HIV-1 Infection Can Determine Long-Term Disease Outcome. J. Virol., 88(21):12793-12801, Nov 2014. PubMed ID: 25165102. Show all entries for this paper.

Displaying record number 54140

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location
Epitope	`LTFGWCFKL`	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 59999

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
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.
LTFGWCFKL had a significantly positive association with HLA C*14; it was recognized by 2/14 C*14-positive subjects and 2/247 C*14-negative subjects.

References

Displaying record number 59398

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef
Epitope	`LTFGWCFKL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	LTNP/EC-4: A03, A11, B35, B51, Cw04, Cw15; LTNP/EC-13: A03, A24, B15, B44, Cw07, Cw14
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, immunodominance

Notes

The study compared B*27/*57-positive versus negative patients among a cohort of long-term nonprogressors and elite controllers with B*27/B*57-negative progressors. Overlapping 15-mers that elicited responses in multiple patients, or were among the strongest responses in a single patient, were narrowed down by truncation to define optimal epitopes, 11 of which were novel.
LTFGWCFKL was recognized by 2/8 LTNP/EC, and 1/2 had it as a dominant response. The restricting HLA (B*15) was predicted, not confirmed experimentally.

References

Migueles2015 Stephen A. Migueles, Daniel Mendoza, Matthew G. Zimmerman, Kelly M. Martins, Sushila A. Toulmin, Elizabeth P. Kelly, Bennett A. Peterson, Sarah A. Johnson, Eric Galson, Kate O. Poropatich, Andy Patamawenu, Hiromi Imamichi, Alexander Ober, Catherine A. Rehm, Sara Jones, Claire W. Hallahan, Dean A. Follmann, and Mark Connors. CD8+ T-Cell Cytotoxic Capacity Associated with Human Immunodeficiency Virus-1 Control Can Be Mediated through Various Epitopes and Human Leukocyte Antigen Types. EBioMedicine, 2(1):46-58, Jan 2015. PubMed ID: 26137533. Show all entries for this paper.

Displaying record number 56988

HXB2 Location	Nef(137-145) DNA(9205..9231)	Nef Epitope Map
Author Location	Nef
Epitope	`LTFGWCFKL`	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, vaccine antigen design

Notes

From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
LTFGWCFKL was a predicted epitope restricted by A2 supertype. 3/31 patient(s) responded to it; none of the responders were known to carry an allele of A2 supertype. Responding patients were infected with HIV clade(s) B, C.

References

Perez2008 Carina L. Pérez, Mette V. Larsen, Rasmus Gustafsson, Melissa M. Norström, Ann Atlas, Douglas F. Nixon, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes. J. Immunol., 180(7):5092-5100, 1 Apr 2008. PubMed ID: 18354235. Show all entries for this paper.

Displaying record number 61664

HXB2 Location	Nef(137-145) DNA(9202..9231)	Nef Epitope Map
Author Location	Nef(137-145)
Epitope	`LTFGWCFKL`	Epitope Alignment
Epitope Name	LL9
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	AC1: A0201, A3001, B3701, B3801, Cw0602, Cw1203; VP1: A0201, A0301, B4101, B5201, Cw0303, Cw1701; AP4: A03, A23, B07, B45; ES3: A25, A68, B51, B57; ES4: A02, A30, B08, B44; ES5: A23, A68, B57, B58; ES9: A02, A30, B27, B57; ES22: A30, A31, B15, B57; ES24: A30, A31, B15, B57; ES31: A03, B27, B58; ES46: A03, B57, B65; ES47: A02, A33, B44, B63; VC1: A23, A29, B07, B39; VC18: A03, A23, B44, B51
Country	United States
Experimental methods	Other, Relative replication capacity assay
Keywords	NK cells, transmission pair

Notes

A transmission pair were studied to compare fitness of HIV isolates between the partners. Virus from both subjects were replication competent and transmissible. The female recipient of virus did not have known protective HLA but protective KIR alleles and was a controller with <100 copies virus/ml during acute infection. Suppressive capacity of her CTLs did not change, but there was a marked decrease in NK cell reponse with the onset of viremic breakthrough at 9 months.
Nef (137-145) LL9, LTFGWCFKL, was present in transmitting subject, VP1 and recipient pre- and post-loss of viremic control. No variant was detected. Presumed restricting alleles were A*02.

References

Walker-Sperling2017 Victoria E. Walker-Sperling, Christopher W. Pohlmeyer, Rebecca T. Veenhuis, Megan May, Krystle A. Luna, Allison R. Kirkpatrick, Oliver Laeyendecker, Andrea L. Cox, Mary Carrington, Justin R. Bailey, Roberto C. Arduino, and Joel N. Blankson. Factors Associated with the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller. EBioMedicine, 16:141-149, Feb 2017. PubMed ID: 28159573. Show all entries for this paper.