Search CTL/CD8+ T-Cell Epitope Database

Found 22 matching records:

Displaying record number 54577

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
		Show epitope variants
Epitope Name	GY9
Subtype	B
Species (MHC/HLA)	human(A*01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A02, B08
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.
In one patient, this epitope GSEELRSLY varied at Y79F to GSEELRSLf, at an anchor position, conferring potent viral escape. One other variant seen was GSEELRSLc.

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 53087

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Species (MHC/HLA)	human(A*01)
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.
3/13 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 57301

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GY9
Subtype	B
Species (MHC/HLA)	(A*01)
Immunogen	peptide-HLA interaction
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Other
Keywords	epitope processing

Notes

Proteasomal cleavage effects on immunodominance were studied using 8 p17 and 11 p24 peptide variants. Epitope abundance due to Antigen processing was the prime influence on CTL dominance while HLA affinity was a moderate influence. Viral mutations modified processing [proteasomal digestion, transporter protein (TAP) affinity, Endoplasmic Reticulum Aminopeptidase (ERAAP) trimming].
Epitope GY9, GSEELRSLY, overlaps epitopes SL9 (SLYNTVATL) and RY11 (RSLYNTVATLY) and may be affected by mutations in these epitopes under study especially since positions R76 and Y79 are anchor residues.
Only immuno-proteasomal digestion generated substantial quantities of GY9.

References

Tenzer2009 Stefan Tenzer, Edmund Wee, Anne Burgevin, Guillaume Stewart-Jones, Lone Friis, Kasper Lamberth, Chih-hao Chang, Mikkel Harndahl, Mirjana Weimershaus, Jan Gerstoft, Nadja Akkad, Paul Klenerman, Lars Fugger, E. Yvonne Jones, Andrew J. McMichael, Søren Buus, Hansjörg Schild, Peter van Endert, and Astrid K. N. Iversen. Antigen Processing Influences HIV-Specific Cytotoxic T Lymphocyte Immunodominance. Nat. Immunol., 10(6):636-646, Jun 2009. PubMed ID: 19412183. Show all entries for this paper.

Displaying record number 61615

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag
Epitope	`GSEELRSLY`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag A01-GY9
Subtype	B
Species (MHC/HLA)	human(A*01)
Immunogen	HIV-1 infection
Patient MHC/HLA	9213: A01, A24, B38, B44, C*04
Country	Germany, Switzerland, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	escape, acute/early infection, assay or method development

Notes

A high throughput whole HIV-1 genome deep sequencing platform combining 454 pyrosequencing with novel assembly and detection of low-frequency variants was used to quantify early stage, poorly represented variants. Application of this method to longitudinal samples from subject 9213 suggests that during acute infection early, low-frequency mutations result from viral adaptation to strong host cellular immune responses during the early decline of peak viral load (VL). Rapid viral escapes from the most dominant immune responses, however, correlate with the loss of this initial viral control.
Non-dominant WT Gag epitope GSEELRSLY was targeted during acute infection in patient 9213 and is present at 100% frequency until d59, 69.2% frequency at d165, back to 100% on d476 and down to 37.8% frequency on d1543.

References

Henn2012 Matthew R. Henn, Christian L. Boutwell, Patrick Charlebois, Niall J. Lennon, Karen A. Power, Alexander R. Macalalad, Aaron M. Berlin, Christine M. Malboeuf, Elizabeth M. Ryan, Sante Gnerre, Michael C. Zody, Rachel L. Erlich, Lisa M. Green, Andrew Berical, Yaoyu Wang, Monica Casali, Hendrik Streeck, Allyson K. Bloom, Tim Dudek, Damien Tully, Ruchi Newman, Karen L. Axten, Adrianne D. Gladden, Laura Battis, Michael Kemper, Qiandong Zeng, Terrance P. Shea, Sharvari Gujja, Carmen Zedlack, Olivier Gasser, Christian Brander, Christoph Hess, Huldrych F. Günthard, Zabrina L. Brumme, Chanson J. Brumme, Suzane Bazner, Jenna Rychert, Jake P. Tinsley, Ken H. Mayer, Eric Rosenberg, Florencia Pereyra, Joshua Z. Levin, Sarah K. Young, Heiko Jessen, Marcus Altfeld, Bruce W. Birren, Bruce D. Walker, and Todd M. Allen. Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection. PLoS Pathog., 8(3):e1002529, 2012. PubMed ID: 22412369. Show all entries for this paper.

Displaying record number 58520

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*01)
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-A*01-restricted p17 optimal epitope GSEELRSLY was tested in a dual color EliSpot and was 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 59747

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GY9
Species (MHC/HLA)	human(A*01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

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.
GSEELRSLY had a significantly positive association with HLA A*01; it was recognized by 11/61 A*01-positive subjects and 6/280 A*01-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 61605

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag
Epitope	`GSEELRSLY`	Epitope Alignment
		Show epitope variants
Epitope Name	A01-GY9 Gag
Species (MHC/HLA)	human(A*01)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	escape

Notes

Proof of principle is given to show that HIV-1 genome sequence from short reads can be used to reconstruct actual whole genome haplotypes including immune escape mutations. 30 whole genome haplotypes from subject 9213 were reconstructed longitudinally and published. Mutations are found to change depending on linkage and resulting clonal interference shows that selection coefficients to study HIV evolution must be estimated for complete haplotypes and not individual escapes.
Subdominant Gag epitope, GY9, GSEELRSLY was present as WT in haplotypes studied, at days 0-1543 i.e. all time points studied, but even at day 0 had begun escape for Patient 9213. Mutations seen were GSEELaSLY (R6A), GSaELRSLY (E3A) and anchor residue change, GSEELRSLf (Y9F).

References

Pandit2014 Aridaman Pandit and Rob J. de Boer. Reliable Reconstruction of HIV-1 Whole Genome Haplotypes Reveals Clonal Interference and Genetic Hitchhiking among Immune Escape Variants. Retrovirology, 11:56, 4 Jul 2014. PubMed ID: 24996694. Show all entries for this paper.

Displaying record number 58366

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	A1 GY9
Subtype	B
Species (MHC/HLA)	human(A*01:01)
Immunogen	in vitro stimulation or selection, HIV-1 infection, 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 GSEELRSLY was successfully used for detection of immune responses for Clades B and C.

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 53821

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17
Epitope	`GSEELRSLY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A*01:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01:01, A03:01, B08:01, B51:01; A01:01, B08:01
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	escape, acute/early infection, characterizing CD8+ T cells

Notes

CTL responses and escape were analyzed in 4 homosexual couples where blood samples were available within weeks of estimated transmission. CTL escape variants were often transmitted. When the recipient had the same HLA type as the donor, CTL escape variants prevented a CTL response to those epitopes in the recipient. Even when the HLA alleles were different in the transmitting couple, a single escape mutation in one epitope can abolish CTL recognition of an overlapping epitope of distinct restriction in the recipient.
The second donor in the study shares A*0101 and B*0801 with his partner. Escape mutations gseeIKsly in GSEELRSLY resulted in 44% reduction in HLA binding affinity and no response in an Elispot assay, and gseeIKsly was the transmitted form.

References

Milicic2005 Anita Milicic, Charles T. T. Edwards, Stéphane Hué, Julie Fox, Helen Brown, Tilly Pillay, Jan W. Drijfhout, Jonathan N. Weber, Edward C. Holmes, Sarah J. Fidler, Hua-Tang Zhang, and Rodney E. Phillips. Sexual Transmission of Single Human Immunodeficiency Virus Type 1 Virions Encoding Highly Polymorphic Multisite Cytotoxic T-Lymphocyte Escape Variants. J. Virol., 79(22):13953-13962, Nov 2005. PubMed ID: 16254331. Show all entries for this paper.

Displaying record number 60950

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A01:01, B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	67200: A01:01, A24:02, B08:01, B57:01, C06:02, C07:01
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.
GSEELRSLY, restricted by A*0101 or B*57, was recognized by 1 patient with the restricting allele.

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 57208

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag
Epitope	`GSEELRSLY`	Epitope Alignment
Species (MHC/HLA)	(A1)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	mother-to-infant transmission

Notes

HIV-1 peptide-specific IFN-γ responses were measured over the first year of life for vertically-infected infants. Late-infected infants (between months 1 and 12) had responses that were more rapid and more focused than those infected before 1 month of life.
1/2 infants tested recognized GSEELRSLY.

References

Lohman-Payne2009 B. Lohman-Payne, J. A. Slyker, B. A. Richardson, C. Farquhar, M. Majiwa, E. Maleche-Obimbo, D. Mbori-Ngacha, J. Overbaugh, S. Rowland-Jones, and G. John-Stewart. Infants with Late Breast Milk Acquisition of HIV-1 Generate Interferon-gamma Responses More Rapidly than Infants with Early Peripartum Acquisition. Clin. Exp. Immunol., 156(3):511-517, Jun 2009. PubMed ID: 19438605. Show all entries for this paper.

Displaying record number 59

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Species (MHC/HLA)	human(A1)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

A study of p17 variation considering known p17 epitopes and individuals with known HLA types revealed that p17 evolution is influenced by immune pressure from CTLs.

References

Birk1998 M. Birk, A. Vahlne, A. Sonnerborg, and M. Sallberg. Nonsynonymous Mutations within the Human Immunodeficiency Virus Type 1 p17 Gene Are Clustered to Sequences Binding to the Host Human Leukocyte Antigen Class I Molecules. AIDS Res. Hum. Retroviruses, 14:241-248, 1998. PubMed ID: 9491914. Show all entries for this paper.

Displaying record number 1367

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79 HXB2)
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GSE
Subtype	B
Species (MHC/HLA)	human(A1)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, supervised treatment interruptions (STI), immunodominance, 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.
This epitope was not recognized by the 6/8 study subjects that were HLA-A1.

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 1646

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Species (MHC/HLA)	human(A1)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

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-A1 women, 1/1 HEPS and 3/3 HIV-1 infected women recognized this epitope, and the response was the dominant HLA-A1 response in all cases.

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 52313

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GSE
Species (MHC/HLA)	human(A1)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

Using previously defined epitopes Oxenius2000b,Oxenius2001b in an IFNgamma Elispot assay, 13 chronically HIV-1 infected patients were studied over a period including therapy with supervised 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 53206

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	(71-79 B consensus)
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GY9
Subtype	B
Species (MHC/HLA)	human(A1)
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

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. Three other strong responses that persisted were detected, along with 1 sub-dominant response to GY9.

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 53502

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GL9
Subtype	B
Species (MHC/HLA)	human(A1)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A3, B57, B7, Cw6, Cw7
Country	United States
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.
One escape mutation, at position 9, gseelrslF, was found in the most polymorphic residue in the epitope. These were shared between clades B and C.

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 53684

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17
Epitope	`GSEELRSLY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A1)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A1, B55, B8, Cw3, Cw7; M12259: A01, B08, B55, C03, C*07
Country	Democratic Republic of the Congo
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 D Gag. The autologous epitope sequence had dramatic changes, the epitope GSEELRSLY peptide was GtegikSLh, and so likely not the actual reactive epitope in the larger peptide.

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 58

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	p17(71-79 LAI)
Epitope	`GSEELRSLY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A1)
Immunogen
Experimental methods
Keywords

Notes

P. Goulder, pers. comm.

References

Brander1996 Christian Brander and Bruce Walker. The HLA-Class I Restricted CTL Response in HIV-1 Infection: Systematic Identification of Optimal Epitopes. In The HLA-Class I Restricted CTL Response in HIV-1 Infection: Systematic Identification of Optimal Epitopes. pages IV--50--IV--60. Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, 1996. URL: http://hiv-web.lanl.gov/immunology. Show all entries for this paper.

Displaying record number 59749

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GY9
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

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.
GSEELRSLY had a significantly positive association with HLA B*07; it was recognized by 2/31 B*07-positive subjects and 1/235 B*07-negative subjects.

References

Displaying record number 59748

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag(71-79)
Epitope	`GSEELRSLY`	Epitope Alignment
Epitope Name	GY9
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, chronic infection

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.
GSEELRSLY had a significantly positive association with HLA C*14; it was recognized by 3/14 C*14-positive subjects and 3/266 C*14-negative subjects.

References

Displaying record number 58034

Download this epitope record as JSON.

HXB2 Location	Gag(71-79) p17(71-79) DNA(1000..1026)	Gag Epitope Map
Author Location	Gag
Epitope	`GSEELRSLY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
Patient MHC/HLA	A01:01, A11:01, B15:01, B44:03, C03:04, C16:01
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5), DNA prime with Ad5 boost
Vaccine strain	B clade IIIB, B clade JRFL, B clade CAM-1
Vaccine component	Gag, Nef, Pol

Notes

T-cell epitope response specificities were examined in uninfected subjects who received the Gag/Pol/Nef vaccine used in the Step trial. Variable epitopes were detected more frequently than would be expected from an unbiased sampling. The most conserved epitopes were detected at a lower frequency, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking. This may be a mechanism used by the virus in both contexts to escape effective T-cell surveillance. Development of vaccine strategies that can elicit a greater breadth, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines.
All vacinees had responses to the Gag peptide pool, and most also had responses to the Nef and/or Pol pools. Subsequent mapping using 9mer minipools demonstrated that T-cell epitopes were recognized across the length of all 3 proteins. A total of 105 distinct 9mers were detected, although some of these may have been overlapping 9mers representing a single epitope.
1 vaccinee recognized 9mer GSEELRSLY.

References

Li2011a Fusheng Li, Adam C. Finnefrock, Sheri A. Dubey, Bette T. M. Korber, James Szinger, Suzanne Cole, M. Juliana McElrath, John W. Shiver, Danilo R. Casimiro, Lawrence Corey, and Steven G Self. Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias Towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study. PLoS One, 6(6):e20479, 2011. PubMed ID: 21695251. Show all entries for this paper.