Search CTL/CD8+ T-Cell Epitope Database

Found 8 matching records:

Displaying record number 57809

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef
Epitope	`RPMTYKGAL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*07)
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 RPMTYKGAL was recognized by 7/9 B*07-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 61136

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef(77-85)
Epitope	`RPMTYKGAL`	Epitope Alignment
		Show epitope variants
Epitope Name	RL9
Subtype	B
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	acute/early infection, variant cross-reactivity

Notes

An 11-member cohort of acutely infected patients was studied to find that CTL cross-recognition of variant epitopes during acute infection is absent or poor as opposed to during chronic HIV-infection.
Nef epitope RL9, RPMTYKGAL_77-85,-specific T cells were less cytotoxic to 4/6 RL9 variants than autologous RL9 in acute infection.

References

Du2016 Victor Y. Du, Anju Bansal, Jonathan Carlson, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Kristin Ladell, Stephanie Gras, Tracy M. Josephs, Sonya L. Heath, David A. Price, Jamie Rossjohn, Eric Hunter, and Paul A. Goepfert. HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection. J. Immunol., 196(8):3276-3286, 15 Apr 2016. PubMed ID: 26983786. Show all entries for this paper.

Displaying record number 61132

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef
Epitope	`RPMTYKGAL`	Epitope Alignment
		Show epitope variants
Epitope Name	RL9
Subtype	C
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Intracellular cytokine staining, Other
Keywords	escape, mutation acquisition, HLA associated polymorphism

Notes

A metric to determine degree of HIV adaptation to HLA and HLA profile was developed. It was found that transmission of pre-adapted HIV to recipients with the associated HLA in a population resulted in elevated VL, impaired immunity and CD4+ T cell decline. Also, pre-adaptation of circulating HIV accounts for much of the variation in immune outcome that was previously attributed to HLA alleles.
Transmission was studied in HIV-C chronically-infected subjects from Southern African cohorts. Non-adapted RL9 (RPMTYKGAL) when transmitted to PBMCs elicited a much greater CTL response in an in vitro killing assay than did adapted RFL9 (RPMTFKGAL) when infecting similar PBMC targets.

References

Carlson2016 Jonathan M. Carlson, Victor Y. Du, Nico Pfeifer, Anju Bansal, Vincent Y. F. Tan, Karen Power, Chanson J. Brumme, Anat Kreimer, Charles E. DeZiel, Nicolo Fusi, Malinda Schaefer, Mark A. Brockman, Jill Gilmour, Matt A. Price, William Kilembe, Richard Haubrich, Mina John, Simon Mallal, Roger Shapiro, John Frater, P. Richard Harrigan, Thumbi Ndung'u, Susan Allen, David Heckerman, John Sidney, Todd M. Allen, Philip J. R. Goulder, Zabrina L. Brumme, Eric Hunter, and Paul A. Goepfert. Impact of Pre-Adapted HIV Transmission. Nat. Med., 22(6):606-613, Jun 2016. PubMed ID: 27183217. Show all entries for this paper.

Displaying record number 53412

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef(75-83)
Epitope	`RPMTYKGAL`	Epitope Alignment
		Show epitope variants
Epitope Name	RPM
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A68.1, B07, B35:03, C04:01, C07:02, DQ2, DQ6, DR15, DR17, DR51, DR52
Experimental methods	CD4 T-cell Elispot - IFNγ, CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	rate of progression, immunodominance, escape

Notes

The increase in plasma viral load in a patient that progressed rapidly was preceded by positive selection of viral escape mutations in epitopes targeted by dominant HIV-1-specific CD8+ T-cell responses,and a decrease in HIV-1-specific CD4+ and CD8+ T-cell frequencies. Overall, escape variant epitopes were recognized 0-80% as efficiently as the index peptide, and the relatively efficiency of the variant epitopes increased using PBLs collected after their appearance. No changes were found in viral tropism, replication kinetics and neutralizing antibody titers, so the rapid decline of the patient was attributed to loss of HIV containment due to CTL escape.
This epitope was one of six epitopes found to be under positive selection for escape mutations and was completely replaced by escape variants between days 172 and 635 (rpmtFkgal, rpmSykAal, rpmtykgaV, rpmtykAal). The first two were the most common at day 635, and experimentally shown to be escape.

References

Oxenius2004 Annette Oxenius, David A. Price, Alexandra Trkola, Charles Edwards, Emma Gostick, Hua-Tang Zhang, Philippa J. Easterbrook, Tin Tun, Andrew Johnson, Anele Waters, Edward C. Holmes, and Rodney E. Phillips. Loss of Viral Control in Early HIV-1 Infection Is Temporally Associated with Sequential Escape from CD8+ T Cell Responses and Decrease in HIV-1-Specific CD4+ and CD8+ T Cell Frequencies. J. Infect. Dis., 190(4):713-721, 15 Aug 2004. PubMed ID: 15272399. Show all entries for this paper.

Displaying record number 53522

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef
Epitope	`RPMTYKGAL`	Epitope Alignment
Epitope Name	RL9
Subtype	B
Species (MHC/HLA)	human(B7)
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 4, RPMnYKGAL, was found not to correspond to the most polymorphic residue in the epitope.

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 55976

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef
Epitope	`RPMTYKGAL`	Epitope Alignment
		Show epitope variants
Epitope Name	RL9(Nef)
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	variant cross-reactivity, chronic infection

Notes

49 ART-naive chronically HIV-1 infected Chinese subjects' CTLs were tested with 413 OLPs in IFN-γ assays, determining optimal epitopes specific for Chinese Clade B HIV-1 sequences.
An inverse correlation was found between CTL response and viral load.
Targeted peptides have lower entropy than peptides that are not CTL targeted. This correlation is independent of HLA-restriction.
Author defined HLA-B7-restricted epitope RPMTYKGAL elicited an immune response in Chinese HIV-1 positive subjects as part of peptide QVPLRPMTYKGALDLSHF. This epitope differs from the previously described HLA-B7-restricted epitopes RPMTYKAAL and RPMTYKAAV, at 1 or 2 residues, RPMTYKgAL and RPMTYKgAl.

References

Zhai2008 Song Zhai, Yan Zhuang, Yang Song, Shu Li, Dedong Huang, Wenzhen Kang, Xinhong Li, Qi Liao, Yanhou Liu, Zhongfang Zhao, Yichen Lu, and Yongtao Sun. HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses Against Immunodominant Optimal Epitopes Slow the Progression of AIDS in China. Curr. HIV Res., 6(4):335-350, Jun 2008. PubMed ID: 18691032. Show all entries for this paper.

Displaying record number 54544

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef(77-85)
Epitope	`RPMTYKGAL`	Epitope Alignment
		Show epitope variants
Epitope Name	RL9
Subtype	B
Species (MHC/HLA)	human(B7 supertype)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, acute/early infection, assay or method development, mutation acquisition

Notes

The ability of T cells from early infected subjects to recognize Nef clade B HIV-1 epitope variants was tested using both a consensus peptide panel and a standardized potential T-cell epitope panel (PTE-B). The magnitude and breadth of PTE-optimized peptide panels was significantly higher than CON peptides'. 29 potential epitopic domains were detected in Nef using the PTE peptide set.
2 PTE-B peptide sequences were identified, IPLRPMTYKgAlDLS and VPLRPMTYrAArDLS, containing variants of this consensus epitope sequence RL9, viz. RPMTYKgAL and RPMTYrAAr, both of which elicited IFN-gamma immune responses.
RL9 restriction to HLA-B7 supertype was inferred based on the subject's known HLA type and published MHC Class I restricted CTL epitopes.

References

Malhotra2007a Uma Malhotra, Fusheng Li, Jessica Nolin, Megan Allison, Hong Zhao, James I. Mullins, Steve Self, and M. Juliana McElrath. Enhanced Detection of Human Immunodeficiency Virus Type 1 (HIV-1) Nef-Specific T Cells Recognizing Multiple Variants in Early HIV-1 Infection. J. Virol., 81(10):5225-5237, May 2007. PubMed ID: 17329342. Show all entries for this paper.

Displaying record number 57011

Download this epitope record as JSON.

HXB2 Location	Nef(77-85) DNA(9025..9051)	Nef Epitope Map
Author Location	Nef
Epitope	`RPMTYKGAL`	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.
RPMTYKGAL was a predicted epitope restricted by B7 supertype. 3/31 patient(s) who responded to it; 2 were known to carry an allele of B7 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.