Search CTL/CD8+ T-Cell Epitope Database

Found 19 matching records:

Displaying record number 59946

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(901-909)
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Species (MHC/HLA)	human(B*15:03)
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.
KRKGGIGGY had a significantly positive association with HLA B*1503; it was recognized by 6/15 B*1503-positive subjects and 7/288 B*1503-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 59117

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Integrase
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Species (MHC/HLA)	human(B*27)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	binding affinity, elite controllers

Notes

The mechanisms of protection of HLA-B*57 and -B*27 restricted CTL responses were compared. Differences include: (1) HLA-B*57 but not -B*27 responses are exceptionally high affinity (2) HLA-B*57 responses seem to downregulate CTL responses through other HLA molecules, but -B*27-restricted responses upregulate responses by other host HLA (3) both HLA are protective at distinct times of infection, i.e., B*57 acts early after infection before CD4+ T-cell counts drop below 200 cells/ml, while B*27 effects are seen during chronic infection, after CD4+ T cells have dropped below the 200 cells/ml point. Similarities were that both HLAs' responses were (1) broad (2) not well maintained through disease progression (3) of comparable breadth and magnitude during chronic infection.
29 HLA-B*57 and 19 HLA-B*27-restricted peptides were tested in a cohort of 18 B-27+ and 6 B-57+ individuals (see supplement for list of peptides).
Tetramer decay assays show that the half life for HLA-B*57-peptide complexed with TCR is significantly stronger than that of peptide-HLA-A*02-TCR; however, pHLA-B*27-TCR is not. In patient 8, B*27-KY9(KRKGGIGGY), had a mean fluorescent intensity of t_1/2=257 min while A*02-IV9(ILKEPVHGV)'s was 244 min.

References

Schellens2014 Ingrid M. M. Schellens, Hilde B. Spits, Marjon Navis, Geertje H. A. Westerlaken, Nening M. Nanlohy, Luc E. Coffeng, Neeltje Kootstra, Frank Miedema, Hanneke Schuitemaker, José A. M. Borghans, and Debbie van Baarle. Differential Characteristics of Cytotoxic T Lymphocytes Restricted by the Protective HLA Alleles B*27 and B*57 in HIV-1 Infection. J. Acquir. Immune Defic. Syndr., 67(3):236-245, 1 Nov 2014. PubMed ID: 25171732. Show all entries for this paper.

Displaying record number 59945

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(901-909)
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Species (MHC/HLA)	human(B*27)
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.
KRKGGIGGY had a significantly positive association with HLA B*27; it was recognized by 23/38 B*27-positive subjects and 13/303 B*27-negative subjects.

References

Displaying record number 59112

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Subtype	CRF01_AE
Species (MHC/HLA)	human(B*27)
Immunogen	HIV-1 infection
Patient MHC/HLA	N094: A02:01, A32:01, B13:02, B14:01, C06:02, C08:02; N107: A02:01, A02:01, B27:05, B57:01, C01:02, C06:02
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	dynamics, rate of progression, transmission pair

Notes

A donor-recipient pair infected with HIV subtype CRF01_AE were studied during chronic infection. The male donor (N094) was believed to have acquired HIV infection in Thailand and infected the recipient (N107) in the UK. Both partners were diagnosed more than 2 years later. Both expressed protective HLA alleles, but nonetheless failed to control viremia. Immune responses were studied in the recipient partner, who expressed both B*27 and B*57 alleles.
The patient had a strong EliSpot response to an 18-mer containing epitope KY9, KRKGGIGGY, at 20 months post-diagnosis (more than 2 years post-infection). KY9 does not vary across clades B or CRF01_AE, and remained the same in both donor and recipient.

References

Brener2015 Jacqui Brener, Astrid Gall, Rebecca Batorsky, Lynn Riddell, Soren Buus, Ellen Leitman, Paul Kellam, Todd Allen, Philip Goulder, and Philippa C. Matthews. Disease Progression Despite Protective HLA Expression in an HIV-Infected Transmission Pair. Retrovirology, 12:55, 2015. PubMed ID: 26123575. Show all entries for this paper.

Displaying record number 61639

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Integrase
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	B27-KY9
Subtype	B
Species (MHC/HLA)	human(B*27)
Immunogen	HIV-1 infection
Country	Canada
Experimental methods	Chromium-release assay, Other
Keywords	epitope processing, escape

Notes

HIV-1 escape by an antigen processing mutation was identified and found to show no change in epitope presentation and thus recognition. This HLA-B*27-restricted mutation, HNF-KkKGGIGGY, at position +2, in intraepitopic sequences of epitope KRKGGIGGY, was identified by mass spectrometry, in vitro. KkKGGIGGY alone resulted in severely impaired epitope production. The findings were confirmed in vivo in 1,134 ART-naive subjects.

References

Zhang2012 Shao Chong Zhang, Eric Martin, Mariko Shimada, Sasha Blue Godfrey, Jennifer Fricke, Shirley Locastro, Nicole Y. Lai, Paul Liebesny, Jonathan M. Carlson, Chanson J. Brumme, Oluwatobi Awele Ogbechie, Huabiao Chen, Bruce D. Walker, Zabrina L. Brumme, Daniel G. Kavanagh, and Sylvie Le Gall. Aminopeptidase Substrate Preference Affects HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-Infected Individuals. J. Immunol., 188(12):5924-5934, 15 Jun 2012. PubMed ID: 22586036. Show all entries for this paper.

Displaying record number 55584

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Subtype	B
Species (MHC/HLA)	human(B27)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction

Notes

Peptide prediction programs based on MHC binding, proteasomal cleavage and TAP transport were applied to select novel epitopes absent from the Los Alamos HIV database. 22 novel epitopes were tested by IFN-gamma ELISpot and 19 (11 HLA-B27 restricted, 8 HLA-B57 restricted) induced strong positive responses.
Magnitude of response generated was similar to that of previously identified epitopes, but the number of individuals responding was lower. This could be explained by less stringent HLA-typing of subjects and perhaps high sequence variability within these novel epitopes.
KY9, KRKGGIGGY, is a novel HLA-B27-restricted epitope that elicits a CTL IFN-gamma response significantly higher than that of Los Alamos database peptides.

References

Schellens2008 Ingrid M. M. Schellens, Can Kesmir, Frank Miedema, Debbie van Baarle, and José A. M. Borghans. An Unanticipated Lack of Consensus Cytotoxic T Lymphocyte Epitopes in HIV-1 Databases: The Contribution of Prediction Programs. AIDS, 22(1):33-37, 2 Jan 2008. PubMed ID: 18090389. Show all entries for this paper.

Displaying record number 62462

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(901-909)
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9, Pol KY9
Subtype	B
Species (MHC/HLA)	human(B*27:02)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	Other, Tetramer binding
Keywords	binding affinity, immunodominance, HLA cross-presentation, chronic infection, protective allele

Notes

HLA-B*27:02 is associated with slower disease progression and lower viral loads to a similar or greater degree than protective HLA-B*27:05 which has a 10-fold higher prevalence in some HIV cohorts. These similar protective effects are mediated by differential epitope binding preferences resulting in distinct immunodominant hierarchies of CTL responses for B*27:02 and B*27:05. An optimal immunodominant B*27:02-restricted Nef VW9-specific response was defined.
Pol KY9 (KRKGGIGGY) was subdominant to Nef VW9 (VRYPLTFGW) with about 57% and 100%, respectively, of 7 HLA-B*27:02+ subjects having epitope-specific CTL responses. Pol KY9 was dominant to Gag KK10 (KRWIILGLNK) with about 37% of 7 HLA-B*27:02+ subjects having epitope-specific CTL responses.
Pol KY9 residue 902R (HXB2) was under strong selective pressure in HLA-B*27:02+ subjects with odds ratio of 15 compared to HLA-B*27- subjects.
Consistent with HLA cross-presentation, compared to B*27:02, B*27:05+ subjects had a similar percentage of responders (about 63%) and Pol VW9-MHC avidity. Also, Pol KY9 residues 903K and 908G (HXB2) were shown to be under strong selective pressure in B*27:05+ subjects compared to B*27- subjects.

References

Adland2018 Emily Adland, Matilda Hill, Nora Lavandier, Anna Csala, Anne Edwards, Fabian Chen, Marek Radkowski, Justyna D. Kowalska, Dimitrios Paraskevis, Angelos Hatzakis, Humberto Valenzuela-Ponce, Katja Pfafferott, Ian Williams, Pierre Pellegrino, Persephone Borrow, Masahiko Mori, Jürgen Rockstroh, Julia G. Prado, Beatriz Mothe, Judith Dalmau, Javier Martinez-Picado, Gareth Tudor-Williams, John Frater, Anette Stryhn, Soren Buus, Gustavo Reyes Teran, Simon Mallal, Mina John, Susan Buchbinder, Gregory Kirk, Jeffrey Martin, Nelson Michael, Jacques Fellay, Steve Deeks, Bruce Walker, Santiago Avila-Rios, David Cole, Christian Brander, Mary Carrington, and Philip Goulder. Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection. J. Virol., 92(4), 15 Feb 2018. PubMed ID: 29167337. Show all entries for this paper.

Displaying record number 58962

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Integrase(186-194)
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Subtype	B
Species (MHC/HLA)	human(B*27:05)
Immunogen	HIV-1 infection
Patient MHC/HLA	53617: A02:01, A02:05, B27:05, B49:01, C02:02, C07:01; 20786: A02:01, A11:01, B27:05, B40:02, C02:02, C02:02; 79379: A01:01, B27:05:02G, B52:01:01G, C02:02:02, C*12:02:01G
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.
4/16 conserved epitopes were restricted by favorable HLA alleles, and 3 of those 4 were recognized in all subjects possessing the favorable allele. Only one conserved epitope was recognized by an unfavorable allele.
KY9, KRKGGIGGY, restricted by favorable allele HLA-B*2705, was one of the conserved epitopes that was recognized in all B*27+ subjects - patients 53617 (A*02:01, 02:05; B*27:05, 49:01; C*02:02, 07:01), 20786 (A*02G1, 11:01; B*27:05, 40:02; C*02:02, 02:02) and 79379 (A*01:01, 01:01; B*27:05, 52:01; C*02:01, 12:02).

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 59031

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(186-194 NL4-3)
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9Pol
Subtype	B
Species (MHC/HLA)	human(B*27:05)
Immunogen	HIV-1 infection
Patient MHC/HLA	R039: A01:01, A31:01, B27:05, B57:01, C02:02, C06:02
Country	United Kingdom
Experimental methods	Intracellular cytokine staining, Other
Keywords	cell-line isolated antibody

Notes

Antigen presentation kinetics of 2 protective Gag epitopes (HLA B*5701 restricted KAFSPEVIPMF, KF11, and HLA B*2705-restricted KRWIILGLNK, KK10) were compared to 2 non-immunodominant epitopes (Pol KRKGGIGGY, KY9, and Vpr VRHFPRIWL, VL9, both B*2705-restricted) during one cycle of replication. All but VL9 showed early epitope presentation due to early incoming HIV-1 particles, resulting in rapid CTL activation and infected cell clearance. Early presented epitopes correlated with a higher viral inoculum and elicited greater CTL activation. Results also substantiated the importance of using virus-infected cells for in vitro studies over peptide pulsing.
KY9 was presented early and its presentation does not depend on de novo synthesis of viral proteins during replication, but on incoming, infecting viral particles. A 10-fold decrease in the amount of virus inoculum resulted in a 2-3 fold decrease in % activated CTL.
Comparison of in vitro KY9 peptide pulsing studies to HIV-VLP (virus-like particle) infection of the epitope suggests that the former is at nonphysiological concentrations, 10³ to 10⁵ times higher than actual intracellular processed epitopes, resulting in higher magnitude of CTL activation and polyfunctional profile of cytokine secretion that may mask actual in vivo levels.

References

Kloverpris2013 Henrik N. Kløverpris, Rebecca P. Payne, Jonah B. Sacha, Jane T. Rasaiyaah, Fabian Chen, Masafumi Takiguchi, Otto O. Yang, Greg J. Towers, Philip Goulder, and Julia G. Prado. Early Antigen Presentation of Protective HIV-1 KF11Gag and KK10Gag Epitopes from Incoming Viral Particles Facilitates Rapid Recognition of Infected Cells by Specific CD8+ T Cells. J. Virol., 87(5):2628-2638, Mar 2013. PubMed ID: 23255798. Show all entries for this paper.

Displaying record number 61207

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(901-909)
Epitope	`KRKGGIGGY`	Epitope Alignment
		Show epitope variants
Epitope Name	KY9
Subtype	B
Species (MHC/HLA)	human(B*27:05)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, escape, HLA associated polymorphism

Notes

This review follows protective HLA-I molecules and their conserved p24 Gag epitopes that escape with a fitness cost to viral replicative capacity (VRC). Compensatory viral mutations can correct for VRC loss to different extents. This results in protective HLA losing impact as well as a modest decline in virulence of HIV with reduced VRC.
Epitope KY9, KRKGGIGGY, is restricted by a strongly protective allele, and can be the immunodominant response in some subjects. Escapes are found at R902K, K903R and G908E, and R902K, G908E can predate escape within KK10 (the most common immunodominant epitope).

References

Kloverpris2015a Henrik N. Kløverpris, Alasdair Leslie, and Philip Goulder. Role of HLA Adaptation in HIV Evolution. Front. Immunol., 6:665, 18 Jan 2016. PubMed ID: 26834742. Show all entries for this paper.

Displaying record number 62463

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(901-909)
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9, Pol KY9
Subtype	B
Species (MHC/HLA)	human(B*27:05)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	Other, Tetramer binding
Keywords	binding affinity, immunodominance, HLA cross-presentation, chronic infection, protective allele

Notes

HLA-B*27:02 is associated with slower disease progression and lower viral loads to a similar or greater degree than protective HLA-B*27:05 which has a 10-fold higher prevalence in some HIV cohorts. These similar protective effects are mediated by differential epitope binding preferences resulting in distinct immunodominant hierarchies of CTL responses for B*27:02 and B*27:05. An optimal immunodominant B*27:02-restricted Nef VW9-specific response was defined.
Pol KY9 (KRKGGIGGY) was subdominant to Gag KK10 (KRWIILGLNK) with about 63% and 100%, respectively, of 19 B*27:05+ subjects having epitope-specific CTL responses.
Pol KY9 residues 903K and 908G (HXB2) were shown to be under strong selective pressure in B*27:05+ subjects compared to HLA-B*27- subjects.
Consistent with HLA cross-presentation, compared to B*27:05, B*27:02+ subjects had a similar percentage of responders (about 57%) and Pol VW9-MHC avidity. Also, Pol KY residue 902R was under strong selective pressure in B*27:02+ subjects with odds ratio of 15 compared to B*27- subjects.

References

Displaying record number 56213

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location
Epitope	`KRKGGIGGY`	Epitope Alignment
Species (MHC/HLA)	(B*27:05)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

Noted by R.P. Payne and P.J. Goulder to be an optimal epitope.

References

PayneGoulderPerCom2009 R. P. Payne and P. J. Goulder. Personal communication, 2009. Show all entries for this paper.

Displaying record number 56550

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location
Epitope	`KRKGGIGGY`	Epitope Alignment
Species (MHC/HLA)	(B*27:05)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

Noted by R.P. Payne and P.J. Goulder to be an optimal epitope restricted by B*2705.

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 56552

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Species (MHC/HLA)	human(B*27:05)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*2705 epitope.

References

Displaying record number 57769

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(901-909)
Epitope	`KRKGGIGGY`	Epitope Alignment
		Show epitope variants
Epitope Name	KY9
Subtype	B
Species (MHC/HLA)	human(B*27:05)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining, Other
Keywords	rate of progression, immunodominance, escape, optimal epitope

Notes

HLA B*2705 is associated with slow progression and superior immune control of HIV. CD8+ T-cell responses were characterized in 9 HAART-naive chronically-infected B*2705-positive individuals. A consistent hierarchy was observed, with Gag KK10 and Pol KY9 being immunodominant, and Vpr VL9 being less strongly targeted. It is likely that the two immunodominant responses are important for viral control in B*2705-positive patients.
8/9 B*2705-positive chronically HIV-infected subjects had an immunodominant response to KY9. Truncations were used to confirm the optimal epitope.
3 escape mutations were identified: KkKGGIGGY, KRKGGIGeY, and KRrGGIGGY.

References

Payne2010 Rebecca P. Payne, Henrik Kløverpris, Jonah B. Sacha, Zabrina Brumme, Chanson Brumme, Søren Buus, Stuart Sims, Stephen Hickling, Lynn Riddell, Fabian Chen, Graz Luzzi, Anne Edwards, Rodney Phillips, Julia G. Prado, and Philip J. R. Goulder. Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8+ T Cells. J. Virol., 84(20):10543-10557, Oct 2010. PubMed ID: 20686036. Show all entries for this paper.

Displaying record number 57797

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol
Epitope	`KRKGGIGGY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*27:05)
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 KRKGGIGGY was recognized by 6/7 B*2705-positive HIV-1-infected patients and was considered in this study to be a "high-probability" novel epitope.

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 57998

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location
Epitope	`KRKGGIGGY`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*27:05)
Immunogen	HIV-1 infection
Country	South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	computational epitope prediction, optimal epitope

Notes

A prediction tool, HLArestrictor, was developed to predict minimal epitopes from longer peptides. Minimal epitopes were predicted and validated for 18 EliSpot-positive 18mers.
KRKGGIGGY was predicted from EliSpot-positive 18mer AVFIHNFKRKGGIGGYSA. The epitope was validated in one B*2705-positive HIV-positive individual by tetramer staining.

References

ErupLarsen2011 Malene Erup Larsen, Henrik Kloverpris, Anette Stryhn, Catherine K. Koofhethile, Stuart Sims, Thumbi Ndung'u, Philip Goulder, Søren Buus, and Morten Nielsen. HLArestrictor---A Tool for Patient-Specific Predictions of HLA Restriction Elements and Optimal Epitopes within Peptides. Immunogenetics, 63(1):43-55, Jan 2011. PubMed ID: 21079948. Show all entries for this paper.

Displaying record number 59947

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol(901-909)
Epitope	`KRKGGIGGY`	Epitope Alignment
Epitope Name	KY9
Species (MHC/HLA)	human(C*03)
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.
KRKGGIGGY had a significantly positive association with HLA C*03; it was recognized by 4/44 C*03-positive subjects and 3/244 C*03-negative subjects.

References

Displaying record number 58080

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HXB2 Location	Pol(901-909) Integrase(186-194) DNA(4785..4811)	Pol Epitope Map
Author Location	Pol
Epitope	`KRKGGIGGY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
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.
3 vaccinees recognized 9mer KRKGGIGGY.
Database note: the HLA restriction of this epitope in the database is B*2705. All 3 responders carried B*2705.

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.