Search CTL/CD8+ T-Cell Epitope Database

Found 7 matching records:

Displaying record number 56248

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HXB2 Location	Nef(105-115) DNA(9109..9141)	Nef Epitope Map
Author Location
Epitope	`KRQDILDLWVY`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(C*07:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A23:01, B08:01, B15:10, C07:01, C*16:01
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	rate of progression

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.
Known epitope KRQDILDLWVY is HLA-Cw*0701-restricted. Response to a peptide containing this epitope was detected in a rapid progressor 12 weeks post-infection.

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 56652

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HXB2 Location	Nef(105-115) DNA(9109..9141)	Nef Epitope Map
Author Location	Nef(105-115)
Epitope	`KRQDILDLWVY`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(C*07:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01:01, A23:01, B14:02, B57:01, C07:01, C08:02
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	escape, acute/early infection

Notes

Using overlapping 15-mer peptides, CTL responses to early, acute HIV infection were determined. Early virus escape attributed to CTL response was charted and subsequent clusters of mutations due to NAb targeting were also found.
Five findings made: (i) exact numbers of transmitted HIV-1 actual and potential T cell epitopes were determined (ii) CTL-mediated virus escape occurring as viremia peaks, drops and reaches set point earlier and faster than previously known (iii) CTL responses to some transmitted virus epitopes were lost after early escapes were selected (iv) a few unexplained escapes were probably due to bystander mutations (v) earliest CTL responses cause the decline of VL in acute infection.
This transmitted epitope, KRQDILDLWVY which is part of tested peptide sequence KRQDILDLWVYHTQGYFP, was studied in patient CH58. HLA-Cw*0701 restriction was as found from database.
Escape mutations in KRQDILDLWVY were seen at nonsynonymous changes, K110R and D113E - rRQDILDLWVY and KRQeILDLWVY. Response to pooled mutant peptides was detected, but at 50% of the response to wild type sequence. These mutations might also impact processing (antigen presentation) of downstream epitope, HTQGYFPDWQ.

References

Goonetilleke2009 Nilu Goonetilleke, Michael K. P. Liu, Jesus F. Salazar-Gonzalez, Guido Ferrari, Elena Giorgi, Vitaly V. Ganusov, Brandon F. Keele, Gerald H. Learn, Emma L. Turnbull, Maria G Salazar, Kent J Weinhold, Stephen Moore, CHAVI Clinical Core B, Norman Letvin, Barton F. Haynes, Myron S. Cohen, Peter Hraber, Tanmoy Bhattacharya, Persephone Borrow, Alan S. Perelson, Beatrice H. Hahn, George M. Shaw, Bette T. Korber, and Andrew J. McMichael. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J. Exp. Med., 206(6):1253-1272, 8 Jun 2009. PubMed ID: 19487423. Show all entries for this paper.

Displaying record number 54543

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HXB2 Location	Nef(105-115) DNA(9109..9141)	Nef Epitope Map
Author Location	Nef(105-115)
Epitope	`KRQDILDLWVY`	Epitope Alignment
		Show epitope variants
Epitope Name	KY11
Subtype	B
Species (MHC/HLA)	human(Cw7)
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.
4 additional variants of this epitope, KRQDILDLWVY, were determined using PTE-B - rRQDILDLWVY, KRQeILDLWVY, rRQeILDLWiY, and KRQDILDLWiY. Only the consensus and last variant, KRQDILDLWiY, were found as patient autologous sequences.
HLA-Cw07 restriction for KY11 was presumed based on the subject having the HLA allele and publication in the Los Alamos database.

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 60966

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HXB2 Location	Nef(105-115) DNA(9109..9141)	Nef Epitope Map
Author Location	Nef(105-115)
Epitope	`KRQDILDLWVY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(Cw7)
Immunogen	HIV-1 infection
Patient MHC/HLA	25122: A01:01, A03:01, B07:02, B37:01, C06:02, C07:02
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.
KRQDILDLWVY, restricted by Cw7 , 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 55503

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HXB2 Location	Nef(105-115) DNA(9109..9141)	Nef Epitope Map
Author Location	Nef
Epitope	`KRQDILDLWVY`	Epitope Alignment
Epitope Name	KY11
Subtype	B
Species (MHC/HLA)	human(Cw7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	dynamics, characterizing CD8+ T cells, chronic infection

Notes

T-cells were studied for exhaustion and dysfunction in chronic HIV infection. Polyfunctionality of CTL immune response to HIV-1 decreased with persistence of antigen presence over time in chronic infection. CTL exhaustion can thus be halted by reduction in viral antigen load - either by ART or through escape mutations.
PD-1, marker for activation and apoptosis increases over time, but it decreases when epitope mutations develop. CD127 however, is not impacted by viral escape.
This epitope, KRQDILDLWVY, went from polyfunctional to monofunctional in the response it was able to elicit, without epitope variations as seen in an untreated patient, Ac-211. Previously published HLA-restriction for KY11 is HLA-Cw7.

References

Streeck2008 Hendrik Streeck, Zabrina L. Brumme, Michael Anastario, Kristin W. Cohen, Jonathan S. Jolin, Angela Meier, Chanson J. Brumme, Eric S. Rosenberg, Galit Alter, Todd M. Allen, Bruce D. Walker, and Marcus Altfeld. Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1-Specific CD8+ T Cells. PLoS Med, 5(5):e100, 6 May 2008. PubMed ID: 18462013. Show all entries for this paper.

Displaying record number 55789

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HXB2 Location	Nef(105-115) DNA(9109..9141)	Nef Epitope Map
Author Location	Nef(105-115)
Epitope	`KRQDILDLWVY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, vaccine
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords

Vaccine Details

Vaccine type	DNA
Vaccine strain	B clade
Vaccine component	Gag
Adjuvant	aluminum phosphate

Notes

To check whether unsuccessful vaccines may interfere with normal patient immune response,2 subjects were followed. The first, 00015, was seronegative while receiving vaccination, but later contracted infection. The second, 00016, had temporary sexual contact with subject 00015 and showed symptoms of disease 2 weeks before him. Without treatment, both reached low chronic viremic levels, and showed similar magnitude of immune response.
Similar immune pressure was seen on viral sequences in both patients, over time in Gag, Pol, Nef.
Data suggest that the vaccine failed to prime subject 00015 against HIV infection, but it did not impair ability to naturally contain viremia in comparison with infecting subject 00016.
CTL immune response to consensus sequence KRQDILDLWVY was elicited in subject 00016. Consensus epitope of both subjects was KRQeILDLWVY.

References

Balamurugan2008 Arumugam Balamurugan, Martha J. Lewis, Christina M. R. Kitchen, Michael N. Robertson, John W. Shiver, Eric S. Daar, Jacqueline Pitt, Ayub Ali, Hwee L. Ng, Judith S. Currier, and Otto O. Yang. Primary Human Immunodeficiency Virus Type 1 (HIV-1) Infection during HIV-1 Gag Vaccination. J. Virol., 82(6):2784-2791, Mar 2008. PubMed ID: 18199650. Show all entries for this paper.

Displaying record number 57500

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HXB2 Location	Nef(105-115) DNA(9109..9141)	Nef Epitope Map
Author Location	Nef
Epitope	`KRQDILDLWVY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Australia
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	assay or method development, HLA associated polymorphism, chronic infection

Notes

Standard overlapping subtype B peptides were compared with 'polyallelic peptides' to determine which set could detect a broader range of ELISpot responses. 28 subjects with chronic AIDS were used to test the peptides against protein Nef. Polyallelic peptides were chosen based on relevant epitopes correlating with HLA-restriction and distribution within a subject-population and HLA class I allele-specific polymorphisms of such epitopes were synthesized.
49 overlapping Nef 15-mers were used as the standard peptides. 62 8- to 11-mer peptides were synthesized as the polyallelic set, 24 of which were embedded within the overlapping 15-mers. 61% of patients responded to polyallelic peptides. 7 of 13 'adapted' polyallelic epitopes (i.e. variant optimized epitopes that still might elicit response based on predicted HLA-bindings), elicited responses in >20% of responding subjects. Only 9 of the 62 polyallelic peptides were discussed in the paper though 80% of them elicited CTL response.
Of the 9 non-adapted central Nef epitopes that were part of the polyallelic peptide set, only 2 were able to elicit CTL response. This epitope, KRQDILDLWVY, did not elicit a response in any of the responding subjects.

References

Almeida2010 Coral-Ann M. Almeida, Steven G. Roberts, Rebecca Laird, Elizabeth McKinnon, Imran Ahmad, Niamh M. Keane, Abha Chopra, Carl Kadie, David Heckerman, Simon Mallal, and Mina John. Exploiting Knowledge of Immune Selection in HIV-1 to Detect HIV-Specific CD8 T-Cell Responses. Vaccine, 28(37):6052-6057, 23 Aug 2010. PubMed ID: 20619380. Show all entries for this paper.