Search CTL/CD8+ T-Cell Epitope Database

Found 31 matching records:

Displaying record number 57392

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Subtype	B
Species (MHC/HLA)	human(A*03)
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 RY10 was studied, TCR usage was BV05b and BV09 in patients 00016 and 00072.

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 60133

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(A*03)
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.
RLRPGGKKKY had a significantly positive association with HLA A*03; it was recognized by 34/63 A*03-positive subjects and 53/278 A*03-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 59128

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29 NL4.3)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY9
Subtype	B
Species (MHC/HLA)	human(A*03)
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.
A synthetic 17-mer, RWEKIRLRPGGKKKYKL, 5-RK9-3, containing an A*03-restricted, immunodominant epitope RLRPGGKKKY, RY10, as well as overlapping peptides, immunodominant RLRPGGKKK, RK9, and subdominant peptide KIRLRPGGK, KK9, produced more RK9 faster, along with N- and C- terminal extended versions as well as antitopes, when incubated with monocyte- rather than DC or MP-cytosolic extracts. RK9 and RY10 also accumulate more than KK9.

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 58436

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Subtype	A1
Species (MHC/HLA)	human(A*0301)
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 RLRPGGKKKY from patient ML0415. When Sanger clone-based sequencing was used however, the same functional, immunogenic site output a different consensus epitope of RLRPGGKKK(K/Q)Y.

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 28

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29 LAI)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*0301)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Pers. comm., B. Wilkens and D. Ruhl.

References

Wilkens1999 B. Wilkens and D. Ruhl. Personal communication, 1999. Show all entries for this paper.

Displaying record number 57788

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag
Epitope	`RLRPGGKKKY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*0301)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction, HLA associated polymorphism

Notes

From a large study of HLA-associated polymorphisms, 431 putative epitopes with good EpiPred scores were selected; 320 of these were tested for IFNgamma EliSpot responses in subjects carrying the predicted HLA.
Peptides with response rate >40% (comparable with mean response rate of 33% for known epitopes) and tested in 5 or more individuals with respective HLA were considered in this study as probable novel epitopes and entered in the database. 41 additional "possible" novel epitopes for which either <5 individuals were tested or response rate was below 40%, are not entered in the database.
There was a markedly higher proportion of putative epitopes in Nef, and the Nef epitopes tended to have the most high-magnitude EliSpot responses. Among 33 epitopes that elicited a response in over 40% out of 5 or more individuals tested, over 61% clustered in Nef.
Epitope RLRPGGKKKY was recognized by 8/17 A*0301-positive HIV-1-infected patients.

References

Almeida2011 Coral-Ann M. Almeida, Corine Bronke, Steven G. Roberts, Elizabeth McKinnon, Niamh M. Keane, Abha Chopra, Carl Kadie, Jonathan Carlson, David W. Haas, Sharon A. Riddler, Richard Haubrich, David Heckerman, Simon Mallal, and Mina John. Translation of HLA-HIV Associations to the Cellular Level: HIV Adapts to Inflate CD8 T Cell Responses against Nef and HLA-Adapted Variant Epitopes. J. Immunol., 187(5):2502-2513, 1 Sep 2011. PubMed ID: 21821798. Show all entries for this paper.

Displaying record number 1112

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29 LAI)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*0301)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes this is an A*0301 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 26

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Species (MHC/HLA)	human(A*0301)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Unpublished, C. Jassoy and Beatrice Culman, pers. comm.

References

Brander1995a Christian Brander and Bruce Walker. The HLA-Class I Restricted CTL Response in HIV-1 Infection: Identification of Optimal Epitopes. In The HLA-Class I Restricted CTL Response in HIV-1 Infection: Identification of Optimal Epitopes. pages IV--1--IV--9. Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, 1995. URL: http://hiv-web.lanl.gov/immunology. Show all entries for this paper.

Displaying record number 59122

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17-p24(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Subtype	B
Species (MHC/HLA)	human(A*0301)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining, Tetramer binding
Keywords	binding affinity, TCR usage

Notes

The impact of antigen sensitivity (AgS) and TCR avidity on HIV-suppressive capacity was interrogated using cell lines generated from CTL clones specific for 3 different conserved, immunodominant epitopes and isolated from HIV-1-infected patients. The study encompassed 3 different epitope sequence specificities (QK10 - QVPLRPMTYK, RY10 - RLRPGGKKKY, KK10- KRWIILGLNK), from 2 different HIV-1 proteins (Gag and Nef), 2 restricting HLA classes (HLA-A*0301 and HLA-B*27) and effects on 3 viral strains (LAI, JR-CSF, DH12). AgS (EC₅₀ in EliSpot) and TCR avidity (EC₅₀ of tetramer concentrations) were significantly correlated.
High TCR avidity CTL clones (A3-QK10/A3-RY10/B27-KK10) were found to more efficiently suppress HIV replication than lower TCR avidity clones, within each epitope specificity.
Differential HIV strain-dependent suppressive capacity was seen for various epitope-specific-CTL clones. This could be due to epitope sequence variations or changes in flanking sequence.
A3-RY0-specific clones suppressed all tested strains of HIV (LAI, JR-CSF, DH12) suboptimally. Though these clones displayed higher TCR avidity and AgS than A3-QK10 clones, they were less efficient at suppressing HIV replication. Flanking mutations are seen in both strains JR-CSF and DH12.

References

Lissina2014 Anna Lissina, Solène Fastenackels, Maria C. Inglesias, Kristin Ladell, James E. McLaren, Olivia Briceño, Emma Gostick, Laura Papagno, Brigitte Autran, Delphine Sauce, David A. Price, Asier Saez-Cirion, and Victor Appay. The Link between CD8+ T-Cell Antigen-Sensitivity and HIV-Suppressive Capacity Depends on HLA Restriction, Target Epitope and Viral Isolate. AIDS, 28(4):477-486, 20 Feb 2014. PubMed ID: 24384691. Show all entries for this paper.

Displaying record number 61243

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(A*0301)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, TCR usage

Notes

Recent findings of the HIV-specific TCR repertoire are reviewed here. Epitope RY10, RLRPGGKKKY-CTL avidity correlates with ability of infected individuals to respond to antigen with sensitivity, polyfunctionality and viral suppression.

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 1114

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Species (MHC/HLA)	human(A*0301, A30)
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 A30, and one was A3, and both responded to RLRPGGKKKY.
The A2+ A3 individual also reacted with two other A3.1 epitopes.

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 20

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Two clonal CTL responses were generated in donor 021-BMC (HLA A3/3001, B42/-, Cw17/-) against different optimal versions of this epitope, one nine amino acids long, one ten.
A previously described optimal A3 epitope overlapping this region, KIRLRPGGK, was not recognized by CTL from 021-BMC.

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 54238

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	A3-RY11(p17)
Species (MHC/HLA)	human(A3)
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 57682

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag
Epitope	`RLRPGGKKKY`	Epitope Alignment
		Show epitope variants
Epitope Name	EnvRY10
Subtype	A, B, C, D
Species (MHC/HLA)	human(A3)
Immunogen	vaccine
Patient MHC/HLA	A24, A3, B18, B7, Cw7, Cw7
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	subtype comparisons, vaccine-induced immune responses

Vaccine Details

Vaccine type	DNA prime with Ad5 boost
Vaccine strain	A clade, B clade, C clade

Notes

A DNA/rAD vaccine induced greater HIV-1-specific CD8+ T-cell responses and higher antibody titers, compared to either a DNA or rAD vaccine alone. This boost in recognition increased the frequency of CTL response, but did not affect either functional avidity or recognition pattern much. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition.
1/9 vaccinees (Subject J) had a positive response to this epitope in EliSpot and avidity assays. The minimum epitope was determined from the original 15-mer. It was shown to be a CD8 epitope by ICS assay.
After boost, the responding subject had EliSpot responses to the wild-type epitope only at highest used peptide concentrations (5 µg/ml). Variants RLRPGGKKhY, RLRPGGKKrY, RLRPGGKKqY, and RLRPGGKKrY were also recognized.

References

Koup2010 Richard A. Koup, Mario Roederer, Laurie Lamoreaux, Jennifer Fischer, Laura Novik, Martha C. Nason, Brenda D. Larkin, Mary E. Enama, Julie E. Ledgerwood, Robert T. Bailer, John R. Mascola, Gary J. Nabel, Barney S. Graham, VRC 009 Study Team, and VRC 010 Study Team. Priming Immunization with DNA Augments Immunogenicity of Recombinant Adenoviral Vectors for Both HIV-1 Specific Antibody and T-Cell Responses. PLoS One, 5(2):e9015, 2010. PubMed ID: 20126394. Show all entries for this paper.

Displaying record number 53631

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Species (MHC/HLA)	human(A3, A30, B42, B62)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A3, B44, B7
Country	United States
Experimental methods	Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	HAART, ART

Notes

Evidence of continued viral evolution during HAART therapy despite low viral load was found in 1/5 patients studied.
The epitope RLRPGGKKKY was invariant (18/18 sequences) prior to therapy in the patient that recognized it.

References

Casazza2005a Joseph P. Casazza, Michael R. Betts, Brenna J. Hill, Jason M. Brenchley, David A. Price, Daniel C. Douek, and Richard A. Koup. Immunologic Pressure within Class I-Restricted Cognate Human Immunodeficiency Virus Epitopes during Highly Active Antiretroviral Therapy. J. Virol., 79(6):3653-3663, Mar 2005. PubMed ID: 15731259. Show all entries for this paper.

Displaying record number 60136

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(A*30)
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.
RLRPGGKKKY had a significantly positive association with HLA A*30; it was recognized by 11/43 A*30-positive subjects and 21/204 A*30-negative subjects.

References

Displaying record number 53839

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY10
Species (MHC/HLA)	human(A*30)
Immunogen	HIV-1 infection
Patient MHC/HLA	M-1003: A24, A30, B39, B47, Cw12, Cw17; P-1189: A23, A24, B07, B39, Cw12, Cw17; P-1031: A02, A30, B13, B18, Cw01, Cw05; M-1002: A30, B18, B40, Cw02, Cw*05
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	responses in children, mother-to-infant transmission, escape, acute/early infection, viral fitness and reversion

Notes

CD8 T-cell responses were examined in mother-infant pairs. Escape variants were commonly detected in maternal plasma. Early infant plasma viruses showed heterogeneity of gag and nef gene sequences as well as mother-to-child transmission of CD8 T-cell escape variants. The stability of escape mutants in the infant over time was determined by infant HLA haplotype and viral fitness.
Sequential plasma specimens from infants showed changes in CD8 T-cell epitope sequences, suggesting that infants are capable of generating virus-specific CD8 T-cell responses.
RLRPGGKKKY was recognized in 2 mothers, and is an A*30 epitope. The variant RLRPGGKKqY was found in 9/10 of one mother's sequences (M-1003). This form was transmitted to her child (P-1189) and was stable by month 12. RLRPGGKKqY was not recognized on ELISPOT assays using maternal PBMC.
RLRPGGKKrY was the form found in the other mother (M-1002). The variant gradually diminished in frequency in her child (P-1031), 10/10 sequences at 2 months, 9/10 at 4 months, and 6/10 at 12 months. This form was recognized as well as wild-type epitope by A*30 infant.

References

Sanchez-Merino2005 Victor Sanchez-Merino, Siwei Nie, and Katherine Luzuriaga. HIV-1-Specific CD8+ T Cell Responses and Viral Evolution in Women and Infants. J. Immunol., 175(10):6976-6986, 15 Nov 2005. PubMed ID: 16272358. Show all entries for this paper.

Displaying record number 58760

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	Gag-RY10
Subtype	B
Species (MHC/HLA)	human(B*15)
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*15-restricted Gag-RY10-specific CTL were used in this study.

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 60134

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(B*1501)
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.
RLRPGGKKKY had a significantly positive association with HLA B*1501; it was recognized by 13/20 B*1501-positive subjects and 40/258 B*1501-negative subjects.

References

Displaying record number 60139

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
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.
RLRPGGKKKY had a significantly positive association with HLA B*1540; it was recognized by 1/1 B*1540-positive subjects and 5/126 B*1540-negative subjects.

References

Displaying record number 25

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29 IIIB)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Species (MHC/HLA)	human(B42)
Immunogen	HIV-1 infection
Experimental methods
Keywords	responses in children, mother-to-infant transmission

Notes

Epitope defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study.
RLRPGGKKRY, a naturally occurring variant, was found in non-transmitting mother and is recognized.
Binds HLA-A3 and Bw62 as well.

References

Walkerpercom1996 C. Wilson, B. Wilkes, D. Ruhl, and B. Walker. Personal communication, 1996. Defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study. Personal communication. Show all entries for this paper.

Displaying record number 1447

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Species (MHC/HLA)	human(B42, B62)
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 60141

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(B*44)
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.
RLRPGGKKKY had a significantly positive association with HLA B*44; it was recognized by 2/23 B*44-positive subjects and 0/79 B*44-negative subjects.

References

Displaying record number 27

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29 LAI)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B62)
Immunogen
Experimental methods
Keywords	review

Notes

Review of HIV CTL epitopes.
Also P. Johnson, pers. comm.

References

McMichael1994 A. J. McMichael and B. D. Walker. Cytotoxic T Lymphocytes Epitopes: Implications for HIV Vaccine. AIDS, 8S:S155-S173, 1994. Comprehensive review summarizing CTL epitopes that have known HLA type and are fine mapped to indicate epitope boundaries. Anchor residues are indicated when known for different HLA restricted epitopes. Includes a summary of the published literature, as well as much work that was in press or submitted for publication. Show all entries for this paper.

Displaying record number 29

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	p17(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Species (MHC/HLA)	human(B62)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Study tracks and quantifies in vivo migration of neo-marked CD8+ HIV-specific CTL.
Adoptively transferred gene-marked HIV-specific CTL homed to specific lymph node sites, colocalizing within the parafollicular regions of the lymph node adjacent to cells expressing HIV tat-fusion transcripts, indicative of viral replication.
The CTL clones expressed CCR5 and localized among HIV-1 infected cells expressing MIP-1α and MIP-1β, CC-chemokines produced at sites of viral replication, suggesting a possible homing mechanism.
This study provides a methodology for tracking and studying antigen specific CTL in vivo.

References

Brodie2000 S. J. Brodie, B. K. Patterson, D. A. Lewinsohn, K. Diem, D. Spach, P. D. Greenberg, S. R. Riddell, and L. Corey. HIV-Specific Cytotoxic T Lymphocytes Traffic to Lymph Nodes and Localize at Sites of HIV Replication and Cell Death. J. Clin. Invest., 105:1407-1417, 2000. PubMed ID: 10811848. Show all entries for this paper.

Displaying record number 53748

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
		Show epitope variants
Epitope Name	RY10
Subtype	B
Species (MHC/HLA)	human(B62)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01, A11, B08, B15, Cw04, Cw07
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	escape, variant cross-reactivity

Notes

HIV-1-specific CD8 T-cell responses were persistent in the chronic phase of HIV-1 infection, although the responses to some of the epitopes declined despite the persistence of the targeted sequences in vivo. Only 4/14 epitopes were potential CTL escape variants, although strong responses to these epitopes persisted for 6 years. This indicates limited viral evolution within targeted CD8 T-cell epitopes during the chronic phase of infection.
The RY10 variant RLRPGGrKKY was the only form of the epitope detected over a 5 year time period in this person. Elispot reactions were stronger to the autologous form than to RLRPGGKKKY, the B clade consensus form.

References

Koibuchi2005a Tomohiko Koibuchi, Todd M. Allen, Mathias Lichterfeld, Stanley K. Mui, Kristin M. O'Sullivan, Alicja Trocha, Spyros A. Kalams, R. Paul Johnson, and Bruce D. Walker. Limited Sequence Evolution within Persistently Targeted CD8 Epitopes in Chronic Human Immunodeficiency Virus Type 1 Infection. J. Virol., 79(13):8171-8181, Jul 2005. PubMed ID: 15956562. Show all entries for this paper.

Displaying record number 60140

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(C*02)
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.
RLRPGGKKKY had a significantly positive association with HLA C*02; it was recognized by 3/24 C*02-positive subjects and 2/102 C*02-negative subjects.

References

Displaying record number 60137

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(C*06)
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.
RLRPGGKKKY had a significantly positive association with HLA C*06; it was recognized by 9/54 C*06-positive subjects and 6/127 C*06-negative subjects.

References

Displaying record number 60135

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
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.
RLRPGGKKKY had a significantly positive association with HLA C*14; it was recognized by 8/11 C*14-positive subjects and 32/247 C*14-negative subjects.

References

Displaying record number 60138

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag(20-29)
Epitope	`RLRPGGKKKY`	Epitope Alignment
Epitope Name	RY10
Species (MHC/HLA)	human(C*16)
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.
RLRPGGKKKY had a significantly positive association with HLA C*16; it was recognized by 6/23 C*16-positive subjects and 15/181 C*16-negative subjects.

References

Displaying record number 61331

HXB2 Location	Gag(20-29) p17(20-29) DNA(847..876)	Gag Epitope Map
Author Location	Gag
Epitope	`RLRPGGKKKY`	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 RLRPGGKKKY elicited response of 118.3 sfc/million PBMC from participants in the Step HIV-1 vaccine efficacy trial who were uninfected at the time of testing. It was part of 15-mers WEKIRLRPGGKKKYK and RLRPGGKKKYKLKHI.

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.