Search CTL/CD8+ T-Cell Epitope Database

Found 15 matching records:

Displaying record number 59399

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Pol
Epitope	`FKRKGGIGGY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*15)
Immunogen	HIV-1 infection
Patient MHC/HLA	LTNP/EC-21: A01, A02, B15, B81, C08, C18
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, immunodominance

Notes

The study compared B*27/*57-positive versus negative patients among a cohort of long-term nonprogressors and elite controllers with B*27/B*57-negative progressors. Overlapping 15-mers that elicited responses in multiple patients, or were among the strongest responses in a single patient, were narrowed down by truncation to define optimal epitopes, 11 of which were novel.
FKRKGGIGGY was recognized by 4/8 LTNP/EC, and 2/4 had it as a dominant response. The restricting HLA (B*15) was confirmed experimentally.

References

Migueles2015 Stephen A. Migueles, Daniel Mendoza, Matthew G. Zimmerman, Kelly M. Martins, Sushila A. Toulmin, Elizabeth P. Kelly, Bennett A. Peterson, Sarah A. Johnson, Eric Galson, Kate O. Poropatich, Andy Patamawenu, Hiromi Imamichi, Alexander Ober, Catherine A. Rehm, Sara Jones, Claire W. Hallahan, Dean A. Follmann, and Mark Connors. CD8+ T-Cell Cytotoxic Capacity Associated with Human Immunodeficiency Virus-1 Control Can Be Mediated through Various Epitopes and Human Leukocyte Antigen Types. EBioMedicine, 2(1):46-58, Jan 2015. PubMed ID: 26137533. Show all entries for this paper.

Displaying record number 56442

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Integrase
Epitope	`FKRKGGIGGY`	Epitope Alignment
Epitope Name	FY10(Integrase)
Subtype	B
Species (MHC/HLA)	human(B15)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	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.
Although the tested peptide sequence contains the exact sequence of a previously described HLA-B15 optimal epitope, FKRKGGIGGY, none of the 21 HLA-B15 carriers responded to it (author communication and Fig.1).

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 53943

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	( C consensus)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
Mutational patterns in the K4 and G9 residues of FKRKGGIGGY are associated with the presence of the HLA presenting molecule in the host.

References

Kiepiela2007 Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Isobella Honeyborne, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Khan, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, Noel McCarthy, Christian Brander, Gerald H. Learn, David Nickle, Christine Rousseau, Hoosen Coovadia, James I. Mullins, David Heckerman, Bruce D. Walker, and Philip Goulder. CD8+ T-Cell Responses to Different HIV Proteins Have Discordant Associations with Viral Load. Nat. Med., 13(1):46-53, Jan 2007. PubMed ID: 17173051. Show all entries for this paper.

Displaying record number 54184

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Integrase(185-194)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	HLA associated polymorphism

Notes

Publicly available HIV-1 subtype C sequences from South Africa and Botswana were analyzed, and 94 HLA-associated amino acid polymorphisms were found. Many polymorphisms were associated with multiple HLA allele classes. 12% associations were negative: association of virus expression of the consensus amino acid with a specific HLA allele. HLA-B alleles accounted for 50% of associations. 19 HLA-associated polymorphisms were embedded in previously defined epitopes.
FKRKGGIGGY was a previously defined B*1503 presented epitope that encompassed a polymorphism, FKRkGGIGGY, in the fourth position.

References

Boutwell2007 Christian L. Boutwell and M. Essex. Identification of HLA Class I-Associated Amino Acid Polymorphisms in the HIV-1C Proteome. AIDS Res. Hum. Retroviruses, 23(1):165-174, Jan 2007. PubMed ID: 17263647. Show all entries for this paper.

Displaying record number 55076

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Integrase
Epitope	`FKRKGGIGGY`	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, rate of progression, immunodominance

Notes

CTL responses restricted by HLA-B*1503 were analyzed in HIV-1 subtype B and C-infected patients. An association between HLA-B*1503 and reduced viral loads in individuals infected with clade B was found. No such correlation was found in clade C infected subjects inspite of the same immunodominant responses in subjects infected with either subtype. Clade B viral control was associated with several subdominanat CTL epitopes lacking in clade C, suggesting that subdominant responses can contribute to viral control.
FKRKGGIGGY of clades B and C is a potential HLA-B*1503-restricted epitope.

References

Frahm2006 Nicole Frahm, Photini Kiepiela, Sharon Adams, Caitlyn H. Linde, Hannah S. Hewitt, Kaori Sango, Margaret E. Feeney, Marylyn M. Addo, Mathias Lichterfeld, Matthew P. Lahaie, Eunice Pae, Alysse G. Wurcel, Timothy Roach, M Anne. St. John, Marcus Altfeld, Francesco M. Marincola, Corey Moore, Simon Mallal, Mary Carrington, David Heckerman, Todd M. Allen, James I. Mullins, Bette T. Korber, Philip J. R. Goulder, Bruce D. Walker, and Christian Brander. Control of Human Immunodeficiency Virus Replication by Cytotoxic T Lymphocytes Targeting Subdominant Epitopes. Nat. Immunol., 7(2):173-178, Feb 2006. PubMed ID: 16369537. Show all entries for this paper.

Displaying record number 53291

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	( C consensus)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	characterizing CD8+ T cells

Notes

HLA class I restricted CD8+ T-cell responses against HIV-1 were analyzed in African patients. Significantly more responses were shown to be HLA-B restricted. Viral load, CD4 count, and thus rate of disease progression were also associated with HLA-B alleles. In addition, the selection pressure imposed on HIV-1 by HLA-B alleles was shown to be substantially greater than by other alleles.
This epitope was suggested to be the epitope within a longer reactive peptide based on correspondence with a known epitope in the HIV database. Also, a significantly higher frequency of people in the Durban cohort who reacted with the peptide had this HLA type.

References

Kiepiela2004 Photini Kiepiela, Alasdair J. Leslie, Isobella Honeyborne, Danni Ramduth, Christina Thobakgale, Senica Chetty, Prinisha Rathnavalu, Corey Moore, Katja J. Pfafferott, Louise Hilton, Peter Zimbwa, Sarah Moore, Todd Allen, Christian Brander, Marylyn M. Addo, Marcus Altfeld, Ian James, Simon Mallal, Michael Bunce, Linda D. Barber, James Szinger, Cheryl Day, Paul Klenerman, James Mullins, Bette Korber, Hoosen M. Coovadia, Bruce D. Walker, and Philip J. R. Goulder. Dominant Influence of HLA-B in Mediating the Potential Co-Evolution of HIV and HLA. Nature, 432(7018):769-775, 9 Dec 2004. LA-UR 04-5920. PubMed ID: 15592417. Show all entries for this paper.

Displaying record number 56506

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Integrase
Epitope	`FKRKGGIGGY`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

HLA-associated polymorphisms were studied in a cohort of 710 chronic subtype C patients from South Africa. 84 HLA Class I-associated polymorphisms were identified, 73% of them with HLA-B. The viral set points associated with HLA allele correlated with the number of reversions associated with that allele, (HLA-B in Gag, HLA-C in Pol).
FKRKGGIGGY is a previously described HLA-B*1503-restricted epitope (part of Pol(Integrase) reacting peptide MAVFIHNFKRkGGIGGYSAGE) that contains a B*1503-associated reversion at residue K (FKRkGGIGGY).

References

Matthews2008 Philippa C. Matthews, Andrew Prendergast, Alasdair Leslie, Hayley Crawford, Rebecca Payne, Christine Rousseau, Morgane Rolland, Isobella Honeyborne, Jonathan Carlson, Carl Kadie, Christian Brander, Karen Bishop, Nonkululeko Mlotshwa, James I. Mullins, Hoosen Coovadia, Thumbi Ndung'u, Bruce D. Walker, David Heckerman, and Philip J. R. Goulder. Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point. J. Virol., 82(17):8548-8559, Sep 2008. PubMed ID: 18596105. Show all entries for this paper.

Displaying record number 52554

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Integrase(185-194)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

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 59660

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Pol(900-909)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Epitope Name	FY10
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.
FKRKGGIGGY had a significantly positive association with HLA B*1503; it was recognized by 13/15 B*1503-positive subjects and 1/288 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 57989

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location
Epitope	`FKRKGGIGGY`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*15:03)
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.
FKRKGGIGGY was predicted from EliSpot-positive 18mer AVFIHNFKRKGGIGGYSA. The epitope was validated in one B*1503-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 59155

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Pol(900-909)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Epitope Name	FY10-Int
Subtype	C
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Tetramer binding
Keywords	TCR usage, characterizing CD8+ T cells

Notes

Inhibitory receptor [programmed death-1 (PD-1)/lymphocyte activation gene-3 (LAG-3)/ T-cell immunoglobulin and mucin domain-3 (Tim-3)] expression was studied during chronic infection in 128 CTL populations from 32 ART-naive, sub-Saharan, HIV-clade C-infected subjects expressing either HLA-B*1503 or -B*4201. PD-1 was found to vary across epitope specificity whether inter- or intra-subject. PD-1 also varied with different TCR clonotypes even within one HIV-specific CTL population. PD-1 correlates directly with viral load (VL).
CTL specific for FY10-Int, FKRKGGIGGY, a highly variable epitope, were found to lack significant correlation with VL.

References

Kloverpris2014a Henrik N. Kløverpris, Reuben McGregor, James E McLaren, Kristin Ladell, Anette Stryhn, Catherine Koofhethile, Jacqui Brener, Fabian Chen, Lynn Riddell, Luzzi Graziano, Paul Klenerman, Alasdair Leslie, Søren Buus, David A. Price, and Philip Goulder. Programmed Death-1 Expression on HIV-1-Specific CD8+ T Cells Is Shaped by Epitope Specificity, T-Cell Receptor Clonotype Usage and Antigen Load. AIDS, 28(14):2007-2021, 10 Sep 2014. PubMed ID: 24906112. Show all entries for this paper.

Displaying record number 57581

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Integrase(185-194)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Epitope Name	FY10
Subtype	B
Species (MHC/HLA)	(B*27)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

Responses to specific B57/58, B27, and B35-restricted epitopes were tested in a cohort of 45 subjects during primary infection. The presence of certain B57/58, B27, and B35-restricted T-cell responses during primary infection better defined disease progression than the HLA genotype alone, suggesting that it is the HIV-specific CD8+ T-cells and not the presence of a particular HLA allele, that determine disease progression.
4/7 B27-positive subjects responded to FKRKGGIGGY, and 26% of the patients' total response magnitude was derived from this specific response.
This epitope was 86% conserved among M-group sequences and 80% conserved among B-subtype sequences.
Epitope-specific HLA-B responses to KK10 and FY10 delayed declines in CD4+ T-cell counts more than 8 years in HLA-B27-positive subjects.

References

Dinges2010 Warren L. Dinges, Julia Richardt, David Friedrich, Emilie Jalbert, Yi Liu, Claire E. Stevens, Janine Maenza, Ann C. Collier, Daniel E. Geraghty, Jeremy Smith, Zoe Moodie, James I. Mullins, M. Juliana McElrath, and Helen Horton. Virus-Specific CD8+ T-Cell Responses Better Define HIV Disease Progression than HLA Genotype. J. Virol., 84(9):4461-4468, May 2010. PubMed ID: 20147397. Show all entries for this paper.

Displaying record number 59661

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Pol(900-909)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Epitope Name	FY10
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.
FKRKGGIGGY had a significantly positive association with HLA B*27; it was recognized by 24/38 B*27-positive subjects and 14/303 B*27-negative subjects.

References

Displaying record number 57944

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Integrase(185-194)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Epitope Name	FY10
Subtype	A1, B, C
Species (MHC/HLA)	human(B*27:05)
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	adenovirus
Vaccine strain	B clade HXB2, A clade 92RW020, C clade 97ZA012
Vaccine component	Env, Gag-Pol

Notes

The study evaluated vaccine-induced T-cell responses in 40 uninfected volunteers. 12 epitopes were targeted. Certain HLA alleles (B27, B57, B35, B14) were preferentially utilized, while other alleles (A02, B07) were rarely utilized. This preference was explained by 4 factors: higher affinity of specific peptides to specific HLAs, higher avidity of certain T-cell receptors, HLA and peptide interactions, and higher surface expression of certain HLAs.
4/4 B*2705-positive vaccinees responded to FKRKGGIGGY. This epitope sequence is an exact match for 86% of M-clade and 80% of B-clade sequences in the LANL HIV sequence database.

References

Friedrich2011 David Friedrich, Emilie Jalbert, Warren L. Dinges, John Sidney, Alex Sette, Yunda Huang, M. Juliana McElrath, and Helen Horton. Vaccine-Induced HIV-Specific CD8+ T Cells Utilize Preferential HLA Alleles and Target-Specific Regions of HIV-1. J. Acquir. Immune Defic. Syndr., 58(3):248-252, 1 Nov 2011. PubMed ID: 21709567. Show all entries for this paper.

Displaying record number 59662

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HXB2 Location	Pol(900-909) Integrase(185-194) DNA(4782..4811)	Pol Epitope Map
Author Location	Pol(900-909)
Epitope	`FKRKGGIGGY`	Epitope Alignment
Epitope Name	FY10
Species (MHC/HLA)	human(C*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.
FKRKGGIGGY had a significantly positive association with HLA C*01; it was recognized by 1/11 C*01-positive subjects and 0/277 C*01-negative subjects.