Search CTL/CD8+ T-Cell Epitope Database

Found 12 matching records:

Displaying record number 59774

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	Gag(144-152)
Epitope	`HQAISPRTL`	Epitope Alignment
Epitope Name	HL9
Species (MHC/HLA)	human(B*13)
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.
HQAISPRTL had a significantly positive association with HLA B*13; it was recognized by 1/2 B*13-positive subjects and 2/219 B*13-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 56370

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	p24(144-152)
Epitope	`HQAISPRTL`	Epitope Alignment
Epitope Name	HL9
Subtype	B
Species (MHC/HLA)	human(B*15)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
HLA-B*15-associated substitution within optimally defined epitope HQAISPRTL is at positions I4, HQAiSPRTL.

References

Brumme2008 Zabrina L. Brumme, Chanson J. Brumme, Jonathan Carlson, Hendrik Streeck, Mina John, Quentin Eichbaum, Brian L Block, Brett Baker, Carl Kadie, Martin Markowitz, Heiko Jessen, Anthony D. Kelleher, Eric Rosenberg, John Kaldor, Yuko Yuki, Mary Carrington, Todd M. Allen, Simon Mallal, Marcus Altfeld, David Heckerman, and Bruce D. Walker. Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute/Early HIV-1 Infection. J. Virol., 82(18):9216-9227, Sep 2008. PubMed ID: 18614631. Show all entries for this paper.

Displaying record number 62107

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	p24(144-152 NL4-3)
Epitope	`HQAISPRTL`	Epitope Alignment
Species (MHC/HLA)	human(B*15)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	vaccine antigen design, viral fitness and reversion

Notes

Computational models were used to translate published HIV-1 sequence data into quantitative viral fitness landscapes with peaks and valleys, that are a function of the amino acid sequences of its constituent proteins. In this case, Clade B Gag was modeled. Predictions were tested against in vitro fitness measurements and were consistent.
Epitope HQAISPRTL is used as an example where each amino acid position within the epitope is associated with a different energy cost, ΔE, and the greater the cost the higher the fitness penalty. Observed HLA-associated escape positions at I147 are one of the 2 positions (including A146) with the lowest h_i value, i.e. the least energetically costly to change.
Based on fitness costs, the authors created a rank-ordered bar chart called the "Epitope Index" and marked out immunodominant response associations on it. The epitope index reads Gag: (164-172)-B*57; (162-172)-B*57 i.e. KF11; (167-175)-A*26; (260-267)-B*08; (240-249)-B*57 i.e. TW10; (296-306)-B*14; (147-155)-B*57; (349-359)-A*11; (263-272)-B*27; (269-277)-B*15; (145-155)-A*25; (306-316)-B*44, from highest to lowest fitness costs.
Brumme2009 is not annotated in this database as epitopes were not immunologically defined, but the table of polymorphisms is available at https://www.hiv.lanl.gov/content/immunology/pdf/2010/escape_article_supplement.html. and a review of the work is available on the main page, hiv.lanl.gov under 'Tools and Data Sets', "Identifying HLA-Associated Polymorphisms in HIV-1" (PDF).

References

Ferguson2013a Andrew L. Ferguson, Jaclyn K. Mann, Saleha Omarjee, Thumbi Ndung'u, Bruce D Walker, and Arup K. Chakraborty. Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design. Immunity, 38(3):606-617, 21 Mar 2013. PubMed ID: 23521886. Show all entries for this paper.

Displaying record number 59188

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	p24(12-20 NL4.3)
Epitope	`HQAISPRTL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*15)
Immunogen	HIV-1 infection
Experimental methods	In vitro proteasome digestion, Other
Keywords	epitope processing

Notes

7 HIV protease inhibitors (PIs) were shown to alter not only proteasome but also aminopeptidase activities that generate epitopes for MHC presentation. These inhibitors altered degradation patterns, sensitivity of peptides to degradation, kinetics and amounts of epitope production and therefore recognition by CTLs.
Precursor 3ISW9, HQAISPRTLNAW, precursor to ISW9 was treated with different PIs. Ritonavir and Kaletra reduced production of B*15-restricted HQAISPRTL.

References

Kourjian2014 Georgio Kourjian, Yang Xu, Ijah Mondesire-Crump, Mariko Shimada, Pauline Gourdain, and Sylvie Le Gall. Sequence-Specific Alterations of Epitope Production by HIV Protease Inhibitors. J. Immunol., 192(8):3496-3506, 15 Apr 2014. PubMed ID: 24616479. Show all entries for this paper.

Displaying record number 60620

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	p24(12-20)
Epitope	`HQAISPRTL`	Epitope Alignment
Epitope Name	HL-9
Subtype	B, C
Species (MHC/HLA)	human(B*15:10)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Subtype-specific substitutions in two HIV Gag regions (fragments F1, amino acids (aa) 5-46, and F2 aa 100-143) result in novel adaptations that affect epitope processing efficiency. Consequent low epitope abundance is associated with weak T cell response and greater immune escape and therefore with disease state. Conversely, epitopes from these regions when restricted by certain rare HLA I alleles, are associated with greater production and resulting CTL response, therefore delayed disease progression.
Most epitopes were found to be processed as precursors with N-terminal extensions beyond the optimal epitope. Only 4 epitopes in this region were associated with delayed progression - HLA-B*5701/03-restricted IW9 (ISPRTLNAW), KF11 (KAFSPEVIPMF), TW10 (TSTLQEQIGW) and HLA-B*2705-restricted KK10 (KRWIILGLNK).
Regardless of ethnic group, white or African, a significant three-way interaction was found between HLA allelic frequency, epitope yield and ethnicity for epitopes of N-terminal fragment F1 (NF1) and C-terminal as well as middle F2 (CF2 and MF2). C-terminal F1 (CF1) epitope yields however, showed a significant difference between ethnic groups. Also, for identical HLA-mediated selection pressure in both Africans and whites, HIV-C had a lower concentration than HIV-B, especially at lower HLA allelic frequencies.
Epitope HQAISPRTL, HL-9, is from fragment F1, and restricted by HLA-B*15, B*1510. 59% NLQGQMVHQAISPRTL, HL-9's subtype B, natural processed epitope form, accumulated after 4 hours processing by constitutive proteasomes, and 56% with immuno proteasomal processing. For subtype C, the natural processed form was NLQGQMVHQAISPRTL, 68% 4h post-constitutive- and 67% post-immuno-proteasomal processing.

References

Tenzer2014 Stefan Tenzer, Hayley Crawford, Phillip Pymm, Robert Gifford, Vattipally B. Sreenu, Mirjana Weimershaus, Tulio de Oliveira, Anne Burgevin, Jan Gerstoft, Nadja Akkad, Daniel Lunn, Lars Fugger, John Bell, Hansjörg Schild, Peter van Endert, and Astrid K. N. Iversen. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification. Cell Rep., 7(2):448-463, 24 Apr 2014. PubMed ID: 24726370. Show all entries for this paper.

Displaying record number 54126

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location
Epitope	`HQAISPRTL`	Epitope Alignment
Species (MHC/HLA)	human(B*15:10)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes that this is an B*1510 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 59771

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	Gag(144-152)
Epitope	`HQAISPRTL`	Epitope Alignment
Epitope Name	HL9
Species (MHC/HLA)	human(B*39)
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.
HQAISPRTL had a significantly positive association with HLA B*39; it was recognized by 8/23 B*39-positive subjects and 6/229 B*39-negative subjects.

References

Displaying record number 59773

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	Gag(144-152)
Epitope	`HQAISPRTL`	Epitope Alignment
Epitope Name	HL9
Species (MHC/HLA)	human(B*42:01)
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.
HQAISPRTL had a significantly positive association with HLA B*4201; it was recognized by 3/8 B*4201-positive subjects and 3/221 B*4201-negative subjects.

References

Displaying record number 59772

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	Gag(144-152)
Epitope	`HQAISPRTL`	Epitope Alignment
Epitope Name	HL9
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, 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.
HQAISPRTL had a significantly positive association with HLA C*06; it was recognized by 20/89 C*06-positive subjects and 14/252 C*06-negative subjects.

References

Displaying record number 135

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	Gag(146-154)
Epitope	`HQAISPRTL`	Epitope Alignment
Species (MHC/HLA)	chimpanzee(Patr-B*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Certain HLA-alleles have been associated with long-term survival -- among them are HLA-B*27 and HLA-B*57.
Of more than 150 chimpanzees that have been reported to be infected with HIV-1, only one has developed AIDS.
CTL responses were studied in two HIV-1 infected chimpanzees that have strong CTL responses, and they were found to respond to highly conserved epitopes that are recognized in humans in the context of HLA-B*27 and HLA-B*57.
The human HLA protein which presents this Patr-B*02 epitope is HLA-B*5701 but the amino acid sequences in the binding pockets of HLA-B*5701 and Patr-B*02 are distinctive.

References

Balla1999b S. S. Balla-Jhagjhoorsingh, G. Koopman, P. Mooij, T. G. Haaksma, V. J. Teeuwsen, R. E. Bontrop, and J. L. Heeney. Conserved CTL epitopes shared between HIV-infected human long-term survivors and chimpanzees. J. Immunol., 162:2308-14, 1999. PubMed ID: 9973508. Show all entries for this paper.

Displaying record number 58021

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	Gag
Epitope	`HQAISPRTL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
Patient MHC/HLA	A02:01, A24:02, B14:02, B39:01, C08:02, C12:03; A02:01, A03:01, B07:02, B39:01, C07:02, C12:03
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.
2 vaccinees recognized 9mer HQAISPRTL.
Database note: The HLA restrictions of this epitope in the LANL database are B*1510, Cw3, and Cw7; 1/2 responders was Cw7-positive.

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.

Displaying record number 62784

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HXB2 Location	Gag(144-152) p24(12-20) DNA(1219..1245)	Gag Epitope Map
Author Location	p24(144-152)
Epitope	`HQAISPRTL`	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, 56 single nucleotide mutations were observed in epitope HQAISPRTL (known to bind to B1510) with a log transformation of mean fitness score, relative to NL4-3, of -0.4645.

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.