Search CTL/CD8+ T-Cell Epitope Database

Found 13 matching records:

Displaying record number 59304

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24
Epitope	`FRDYVDRFYK`	Epitope Alignment
Epitope Name	FK10
Species (MHC/HLA)	human(B*18)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression

Notes

620 patients in early/acute stages of infection were screened for Elispot responses to optimally defined epitopes to find associations between specific CTL responses and long-term control of HIV-1. Seven epitope-specific responses were associated with delayed initiation of ART, and 12 were associated with a more rapid initiation of therapy. While initial viremia, HLA Class I genotype and viral set points were associated, breadth and magnitude of response did not influence early viral set point. A broader CTL response to Gag, however, associates with slower disease progression.
Initial specificity of CTL response rather than restricting HLA-I molecule contributes to disease control.
The HLA-B*18-restricted epitope FRDYVDRFYK was associated with accelerated initiation of ART.

References

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

Displaying record number 1453

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24(161-170)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Species (MHC/HLA)	human(B18)
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 1680

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24(293-302)
Epitope	`FRDYVDRFYK`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B18)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

Variants FRDYVDRF(Y/F)K are specific for the B,D/A,C clades.
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-B18 women, 3/4 HEPS and 1/9 HIV-1 infected women recognized this epitope, likelihood ratio 5.3, p value 0.04, and HEPS women tended to respond to FRDYVDRFY/FK, while infected women tended to respond to YPLTFGWCY/F.
The dominant response to this HLA allele was to this epitope for all 3/4 HEPS cases and for the single HIV-1 infected women that responded to this epitope.
Four epitopes were considered to be ``resistant epitopes'', as they were preferentially reactive in HEPS women and so may confer resistance, and these were found in three different proteins: A2 ILK(D/E)PVHGV in RT, A*6802 DTVLEDINL in Protease, B14 DLNM/TLN(I/V)V in p24 and B18 FRDYVDRF(Y/F)K also in p24.
Differences in epitope specificity were only seen for responses restricted by class I HLA alleles A2, A24, A*6802, B14, and B18, previously shown to be associated with resistance to HIV-1 in this cohort.

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 55497

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24
Epitope	`FRDYVDRFYK`	Epitope Alignment
Epitope Name	FK10
Subtype	B
Species (MHC/HLA)	human(B18)
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.
95 days after first testing, epitope FRDYVDRFYK showed no variation in a treated patient, Ac-84. Previously published HLA-restriction for FK10 is HLA-B18.

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 52425

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24
Epitope	`FRDYVDRFYK`	Epitope Alignment
Subtype	B, D
Species (MHC/HLA)	human, macaque(B18)
Immunogen	HIV-1 infection, vaccine
Experimental methods
Keywords	subtype comparisons, epitope processing, vaccine-induced immune responses, immunodominance

Vaccine Details

Vaccine type	DNA prime with modified vaccinia Ankara (MVA) boost
Vaccine strain	A clade
Vaccine component	p17 Gag, p24 Gag

Notes

The HIV-1 subtype A focused vaccine HIVA contains p24 and p17, in a reversed order relative to the Gag polyprotein to prevent myristylation of p17, which could direct the protein to the cell membrane and inhibit efficient peptide processing and class I presentation, as well as a polyepitope string of conserved, often immunodominant epitopes that were selected to have particularly good cross-reactive potential for the A-clade epidemic in Nairobi, Kenya. A DNA and MVA prime-boost vaccination protocol using the HIVA antigen will be used in a phase III clinical trial in Kenya. This epitope is included in the polyepitope string Hanke2000.
Multiple CD4+ or CD8+ T-cell vaccine-induced responses to peptide pools were detected using intracellular cytokine staining and IFNgamma Elispot assays after vaccination of 5 macaques. The response to the Mamu A*01 SIV p27 epitope p11C (CTPYDINQM), included in the polyepitope region, was not immunodominant in the Mamu A*01 vaccinated macaques, possibly because of processing limitations in context of the artificial polyepitope string Wee2002.

References

Hanke2000 Tomas Hanke and Andrew J. McMichael. Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nat. Med., 6(9):951-955, Sep 2000. PubMed ID: 10973301. Show all entries for this paper.

Wee2002 Edmund G.-T. Wee, Sandip Patel, Andrew J. McMichael, and Tomáš Hanke. A DNA/MVA-Based Candidate Human Immunodeficiency Virus Vaccine for Kenya Induces Multi-Specific T Cell Responses in Rhesus Macaques. J. Gen. Virol., 83(Pt 1):75-80, Jan 2002. PubMed ID: 11752703. Show all entries for this paper.

Displaying record number 59075

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24(161-170)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	PIC1362: A02:01, A25:01, B18:01, B51:01, C01:02, C12:03
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	viral fitness and reversion

Notes

CTL responses were studied in a single drug-naive individual during the first 4 years of infection. 25 CTL epitopes were identified; 17 of them underwent evolution; 15 mutant forms that escaped or partially escaped were detected.
FRDYVDRFYK was a persistent epitope, consistently present during 4 years of infection; no escape mutants were detected.

References

Liu2007a Yi Liu, John McNevin, Hong Zhao, Denis M. Tebit, Ryan M. Troyer, Matthew McSweyn, Ananta K. Ghosh, Daniel Shriner, Eric J. Arts, M. Juliana McElrath, and James I. Mullins. Evolution of Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitopes: Fitness-Balanced Escape. J. Virol., 81(22):12179-12188, Nov 2007. PubMed ID: 17728222. Show all entries for this paper.

Displaying record number 310

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24( subtype B, D)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Subtype	B, D
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*1801 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 54148

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24(161-170 HXB2)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Epitope Name	FK10
Subtype	B
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	PIC1362: A02:01, A25:01, B18:01, B51:01, C01:02, C12:03
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, mutation acquisition, optimal epitope

Notes

T-cell immunity and the impact of selection were longitudinally studied in a patient from the time of transmission. New epitopes were detected at sites that were shown to be under positive selection. Env was found to be the major target of CTLs and most of the new epitopes were found here. One third of the sites examined were associated with epitope escape mutations from CTL. Acquisition of mutations found at high frequency in the database was suggested to be a result of reversion of CTL epitopes in the absence of immune targeting.

References

Liu2006 Yi Liu, John McNevin, Jianhong Cao, Hong Zhao, Indira Genowati, Kim Wong, Sherry McLaughlin, Matthew D. McSweyn, Kurt Diem, Claire E. Stevens, Janine Maenza, Hongxia He, David C. Nickle, Daniel Shriner, Sarah E. Holte, Ann C. Collier, Lawrence Corey, M. Juliana McElrath, and James I. Mullins. Selection on the Human Immunodeficiency Virus Type 1 Proteome following Primary Infection. J. Virol., 80(19):9519-9529, Oct 2006. PubMed ID: 16973556. Show all entries for this paper.

Displaying record number 309

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24( subtype B, D)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Subtype	B, D
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Noted in Brander 1999, this database, to be B*1801, FRDYVDRFY.

References

Ogg1998b G. S. Ogg, T. Dong, P. Hansasuta, L. Dorrell, J. Clarke, R. Coker, G. Luzzi, C. Conlon, A. P. McMichael, and S. Rowland-Jones. Four Novel Cytotoxic T-Lymphocyte Epitopes in the Highly Conserved Major Homology Region of HIV-1 Gag, Restricted through B*4402, B*1801, A*2601, B*70 (B*1509). AIDS, 12:1561-1563, 1998. PubMed ID: 9727585. Show all entries for this paper.

Displaying record number 58140

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24(161-170)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Epitope Name	FK10
Subtype	B
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	PIC1362: A02:01, A25:01, B18:01, B51:01, C01:02, C12:03
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, acute/early infection

Notes

CTL responses were studied in a drug-naive patient for 4 years, beginning at the time of infection. CTL recognition of 25 epitopes was observed, and 18 of them underwent mutational changes, usually indicative of escape.
The sequence of FRDYVDRFYK remained unchanged during 4 years of infection.

References

Liu2011a Yi Liu, John P. McNevin, Sarah Holte, M. Juliana McElrath, and James I. Mullins. Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection. PLoS One, 6(1):e15639, 2011. PubMed ID: 21283794. Show all entries for this paper.

Displaying record number 54353

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24
Epitope	`FRDYVDRFYK`	Epitope Alignment
Epitope Name	B18-FK10(p24)
Species (MHC/HLA)	human(B27)
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 contributions of immune responses restricted to individual HLA class I molecules were studied.
This epitope-HLA combination was recognized. The most frequently recognized 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 contributions 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 62304

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24(293-302)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Epitope Name	FK10
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	acute/early infection, mutation acquisition, viral fitness and reversion, viral replication

Notes

In a longitudinal study of patient 1362, escape mutations were tracked in 5 HIV Env gp120 and 2 Gag p24 CTL epitopes. Only 1/9 gp120 dominant mutations that appeared during acute infection within one year had fitness loss, 4/9 had no effect on fitness and 3/9 experienced a slight fitness increase. Meanwhile, all 4 Gag p24 mutations, which appeared in two years, decreased fitness! Thus, Gag p24 mutations are associated with significant fitness cost, but most Env escapes are fitness-neutral.
Despite strong CTL response to Gag p24 epitope FK10 during the first 1035 DPS (days post symptoms), no mutations in FK10 emerged over 3 years.

References

Troyer2009 Ryan M. Troyer, John McNevin, Yi Liu, Shao Chong Zhang, Randall W. Krizan, Awet Abraha, Denis M. Tebit, Hong Zhao, Santiago Avila, Michael A. Lobritz, M. Juliana McElrath, Sylvie Le Gall, James I. Mullins, and Eric J. Arts. Variable Fitness Impact of HIV-1 Escape Mutations to Cytotoxic T Lymphocyte (CTL) Response. PLoS Pathog., 5(4):e1000365, Apr 2009. PubMed ID: 19343217. Show all entries for this paper.

Displaying record number 62814

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HXB2 Location	Gag(293-302) p24(161-170) DNA(1666..1695)	Gag Epitope Map
Author Location	p24(293-302)
Epitope	`FRDYVDRFYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	assay or method development, protective allele

Notes

NL4-3 Gag polyprotein random mutagenesis, high-throughput fitness profiling and in silico prediction of MHC-peptide binding affinity revealed that mutations in CTL epitopes presented by protective MHC-I alleles, vs. non-protective alleles, showed greater loss of experimental replicative capacity and lower levels of predicted reduction in MHC-I binding affinity. Together, these two variables could predict protectiveness of MHC-I alleles in a linear regression model. Analyses of intraperson viral evolution in 4 LTNP vs. 4 paired progressor subjects further supported paper conclusions.
After mutagenesis and passaging through human T cells, 69 single nucleotide mutations were observed in epitope FRDYVDRFYK (known to bind to B1801) with a log transformation of mean fitness score, relative to NL4-3, of -0.7609.

References

Du2017 Yushen Du, Tian-Hao Zhang, Lei Dai, Xiaojuan Zheng, Aleksandr M. Gorin, John Oishi, Ting-Ting Wu, Janice M. Yoshizawa, Xinmin Li, Otto O. Yang, Otoniel Martinez-Maza, Roger Detels, and Ren Sun. Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes. mBio, 8(6), 28 Nov 2017. PubMed ID: 29184023. Show all entries for this paper.