Search CTL/CD8+ T-Cell Epitope Database

Found 13 matching records:

Displaying record number 59826

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Pol(850-858)
Epitope	`IQQEFGIPY`	Epitope Alignment
Epitope Name	IY9
Species (MHC/HLA)	human(A*34)
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.
IQQEFGIPY had a significantly positive association with HLA A*34; it was recognized by 1/7 A*34-positive subjects and 0/281 A*34-negative subjects.
IQQEFGIPY was significantly nonprotective, associated with HIV chronic disease progression when restricted by HLA-A*34 in a cohort of 245 controllers and 96 progressors.

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 56453

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Integrase
Epitope	`IQQEFGIPY`	Epitope Alignment
Epitope Name	IY9(Integrase)
Subtype	B
Species (MHC/HLA)	human(B15)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	enhancing activity, non-susceptible form, 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.
The tested peptide sequences, KAACWWAGIKQEFGIPY and GIKQEFGIPYNPQSQGVV, contain a variant, IkQEFGIPY that differs by 1 substitution from the previously described HLA-B15 epitope IQQEFGIPY. None of the 21 HLA-B15 carriers responded to the variant IkQEFGIPY.

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 59825

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Pol(850-858)
Epitope	`IQQEFGIPY`	Epitope Alignment
Epitope Name	IY9
Species (MHC/HLA)	human(B*15:01)
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.
IQQEFGIPY had a significantly positive association with HLA B*1501; it was recognized by 3/26 B*1501-positive subjects and 1/288 B*1501-negative subjects.
IQQEFGIPY was significantly nonprotective, associated with HIV chronic disease progression when restricted by HLA-B*1501 in a cohort of 245 controllers and 96 progressors.

References

Displaying record number 55074

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Integrase
Epitope	`IQQEFGIPY`	Epitope Alignment
Subtype	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.
IQQEFGIPY of clade 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 57988

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location
Epitope	`IQQEFGIPY`	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.
IQQEFGIPY was predicted from EliSpot-positive 18mer VKAACWWAGIQQEFGIPY. 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 59154

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Pol(850-858)
Epitope	`IQQEFGIPY`	Epitope Alignment
Epitope Name	IY9-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 IY9-Int, IQQEFGIPY, 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 53942

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	( C consensus)
Epitope	`IQQEFGIPY`	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 Q2 residue of IQQEFGIPY 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 54125

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location
Epitope	`IQQEFGIPY`	Epitope Alignment
Species (MHC/HLA)	human(B*15:03)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes that this is an B*1503 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 54190

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Integrase(135-143)
Epitope	`IQQEFGIPY`	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.
IQQEFGIPY was a previously defined B*1503 presented epitope that encompassed a polymorphism, IqQEFGIPY, in the second 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 62156

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Integrase(135-143)
Epitope	`IQQEFGIPY`	Epitope Alignment
Epitope Name	IY9
Subtype	A1, D
Species (MHC/HLA)	human(B*15:03)
Immunogen	HIV-1 infection
Country	Uganda
Experimental methods	HLA binding, Relative replication capacity assay
Keywords	subtype comparisons, escape, HLA associated polymorphism

Notes

HLA associated-HIV adaptation is studied for the first time in the Ugandan (East African) context in 464 ART-naive, AIDS patients chronically infected with HIV-1 A1 or D. Most HIV-associated polymorphisms were previously identified in other subtypes, but 34% of these were differentially selected between subtypes A1 and D. Subtype-specific variants were found to be due to effects on epitope-HLA binding (recognition) or fitness cost barriers to escape.
A novel Nef epitope was also discovered and immunologically verified.
Int epitope IQQcFGIPYT was used as a positive control in a competitive binding assay with HLA-B*1503. It differes from the published epitope IQQEFGIPYT to contain a C upon which the fluorophore was conjugated.

References

Kinloch2019 Natalie N. Kinloch, Guinevere Q. Lee, Jonathan M. Carlson, Steven W. Jin, Chanson J. Brumme, Helen Byakwaga, Conrad Muzoora, Mwebesa B. Bwana, Kyle D. Cobarrubias, Peter W. Hunt, Jeff N. Martin, Mary Carrington, David R. Bangsberg, P. Richard Harrigan, Mark A. Brockman, and Zabrina L. Brumme. Genotypic and Mechanistic Characterization of Subtype-Specific HIV Adaptation to Host Cellular Immunity. J. Virol., 93(1), 1 Jan 2019. PubMed ID: 30305354. Show all entries for this paper.

Displaying record number 59824

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Pol(850-858)
Epitope	`IQQEFGIPY`	Epitope Alignment
Epitope Name	IY9
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.
IQQEFGIPY had a significantly positive association with HLA B*39; it was recognized by 7/27 B*39-positive subjects and 4/314 B*39-negative subjects.
IQQEFGIPY was significantly nonprotective, associated with HIV chronic disease progression when restricted by HLA-B*39 in a cohort of 245 controllers and 96 progressors.

References

Displaying record number 62895

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HXB2 Location	Pol(850-858) Integrase(135-143)	Pol Epitope Map
Author Location	Integrase(135-143)
Epitope	`IQQEFGIPY`	Epitope Alignment
		Show epitope variants
Epitope Name	IY9
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	vaccine antigen design

Notes

Single nucleotide mutations were introduced onto a patient-derived subtype C reverse transciptase (RT)-integrase sequence (SK-278, 98.2% similar to consensus C) on a subtype B NL4-3ΔRT-integrase backbone and assessed for their impact on in vitro viral replicative capacity (RC) in a GFP-based assay. Structural modeling of the RT mutations that mediated the greatest RC reductions (A158S, V241I, & I257V) provided insight into functional consequences.
Relative to NL4-3 recombinant virus encoding wild-type SK-278 RT-integrase, the introduction of integrase mutation Q136K did not mediate a significant reduction in RC.
Q136K is located within well-defined epitope IQQEFGIPY (IY9, known to bind to B*1503) and is also 4 AA downstream of STTVKAACWW (NL4-3)/ SAAVKAACWW (SK-278).

References

Ojwach2021 Doty B. A. Ojwach, Paradise Madlala, Michelle Gordon, Thumbi Ndung'u, and Jaclyn K. Mann. Vulnerable targets in HIV-1 Pol for attenuation-based vaccine design. Virology, 554:1-8 doi, Feb 2021. PubMed ID: 33316731 Show all entries for this paper.

Displaying record number 62852

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HXB2 Location	Pol(850-858) Integrase(135-143) DNA(4632..4658)	Pol Epitope Map
Author Location	Integrase(135-143)
Epitope	`IQQEFGIPY`	Epitope Alignment
Epitope Name	IY9
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	acute/early infection, HLA associated polymorphism, chronic infection, protective allele

Notes

The in vitro replicative capacity (RC) of recombinant subtype B NL4-3 viruses expressing subtype C RT-integrase sequences derived from recently infected patients correlated positively with log subsequent VL set point and a higher rate of CD4 decline, while the RC of NL4-3 recombinants expressing subtype C RT-integrase sequences derived from chronically infected patients correlated positively with log VL but negatively with CD4 count. Protective & risk HLA alleles were associated with lower and higher RC values, respectively, and the number of HLA-associated polymorphisms in RT correlated positively with RC while the inverse was observed for integrase. About 90% of RT-integrase polymorphisms significantly associated with altered RC occurred inside or within 5 aa of A-list epitopes (LANL HIV Database).
Integrase polymorphism Q136K was associated with altered RC and is located within well-defined epitope IQQEFGIPY, IY9, known to bind to B*1503.
Q136K occurred in 28 participant-derived recombinant viruses with a median RC of 0.88, while 368 analogous viruses without M357R had a median RC of 0.92, relative to unmodified NL4-3.

References

Ojwach2018 Doty B. A. Ojwach, Daniel MacMillan, Tarylee Reddy, Vladimir Novitsky, Zabrina L. Brumme, Mark A. Brockman, Thumbi Ndung'u, and Jaclyn K. Mann. Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection. J. Virol., 92(19), 1 Oct 2018. PubMed ID: 29997209. Show all entries for this paper.