Search CTL/CD8+ T-Cell Epitope Database

Found 11 matching records:

Displaying record number 53978

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`QATQDVKNW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*53:01)
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.
QATQDVKNW is an optimal epitope.

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 57777

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	Gag(308-316)
Epitope	`QATQDVKNW`	Epitope Alignment
Epitope Name	QW9
Subtype	C
Species (MHC/HLA)	human(B57, B58:01)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Relative replication capacity assay
Keywords	responses in children, rate of progression

Notes

Immunological responses in progressing and slow-progressing C-clade infected infants suggest a link between slow progression and HLA-B*57/5801 epitope-specific Gag mutations of the transmitted virus and not due to coreceptor usage or the presence of Nef deletions/insertions.
All viral isolates studied contained polymorphisms in at least one of the 4 Gag epitopes studied (ISW9, KF11, TW10, QW9).
In a viral replication assay, T cells were infected with wild-type and variants of the 4 Gag epitopes studied (ISW9, KF11, TW10, QW9) and the CypA binding loop. Viruses from progressing infants showed higher replicative capacity than viruses from slow-progressing infants. Thus B*57/5801-related mutations in p24 epitopes may contributed to low replicative capacity.
In 6/8 subjects, the early viral isolates contained variations in TW10 positions 3 and 7 (T3S, T3N, I7V, I7L) that have previously been shown to reduce replicative capacity. In 2/3 progressing infants, mutations in TW10 were accompanied by upstream compensatory changes at H219Q, I223P, and M228I/L.

References

Prado2010 Julia G. Prado, Andrew Prendergast, Christina Thobakgale, Claudia Molina, Gareth Tudor-Williams, Thumbi Ndung'u, Bruce D. Walker, and Philip Goulder. Replicative Capacity of Human Immunodeficiency Virus Type 1 Transmitted from Mother to Child Is Associated with Pediatric Disease Progression Rate. J. Virol., 84(1):492-502, Jan 2010. PubMed ID: 19828603. Show all entries for this paper.

Displaying record number 61622

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	p24
Epitope	`QATQDVKNW`	Epitope Alignment
		Show epitope variants
Epitope Name	B5801-QW9, B57-QW9
Subtype	C
Species (MHC/HLA)	human(B57, B58:01)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	elite controllers

Notes

70 HIV-C-infected ART-naive South African viremic controllers (VC) of whom 50% carried protective HLA-I alleles were studied longitudinally for 5 years to show that mechanism of viral load (VL) control is different between protective-HLA I-carrying and nonprotective-HLA I-carrying VCs. While control by protective HLA-I carrying VCs is driven primarily by broad, anti-Gag CTL responses with potent ex vivo viral inhibition, control in subjects without protective HLA I may be durable but CTL-independent.
Progression in VCs is generally precipitated by CTL escape and lowered antivrial efficacy seen as loss of CTL polyfunctionality, proliferation and ex vivo suppression of HIV-1 replication around virologic failure. Epitopes targeted before and after virologic failure are listed in Tables 2, 3 and 4 on pages 6824, 6825, 6826.
Optimal epitope, QATQDVKNW (QW9) was targeted by subjects SK-187 and SK-224, failing VCs, as well as SK-282, a VC, before and after loss of viremic control (EliSpot = 300/883 and 2760/1940 sfu/10⁶ cells respectively). Subjects SK-089 and SK-282 also targeted QW9 restricted by B*57 and B*5801, only after loss of viremic control (EliSpot = 2175 and 0? sfu/10⁶ cells). SK-282 carried variants of QW9.

References

Koofhethile2016 Catherine K. Koofhethile, Zaza M. Ndhlovu, Christina Thobakgale-Tshabalala, Julia G. Prado, Nasreen Ismail, Zenele Mncube, Lungile Mkhize, Mary van der Stok, Nonhlanhla Yende, Bruce D. Walker, Philip J. R. Goulder, and Thumbi Ndung'u. CD8+ T Cell Breadth and Ex Vivo Virus Inhibition Capacity Distinguish between Viremic Controllers with and without Protective HLA Class I Alleles. J. Virol., 90(15):6818-6831, 1 Aug 2016. PubMed ID: 27194762. Show all entries for this paper.

Displaying record number 57686

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location
Epitope	`QATQDVKNW`	Epitope Alignment
Epitope Name	QW9
Subtype	C
Species (MHC/HLA)	human(B57, B58:01)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	immunodominance, characterizing CD8+ T cells

Notes

The antiviral effectiveness of HLA-B*57/58 and HLA-Cw*07 restricted CD8+ T-cell responses did not differ significantly in polyfunctionality, suggesting that the loss of polyfunctionality during disease progression is independent of the restricting HLA allele. There were no differences in the polyfunctionality of T cells specific to wild type versus mutated epitopes, suggesting that sequence variation does not significantly impact CD8 T-cell polyfunctionality in chronic infection.
3/9 HLA-B*57/58- and HLA-Cw*07-positive subjects had a positive Elispot response to this epitope. Among 37 HLA-B*57/58- and HLA-Cw*07-positive subjects, this epitope was most often presented by HLA-B*5702 and HLA-B*5801, and least presented by HLA-B*5703.

References

Mkhwanazi2010 Nompumelelo Mkhwanazi, Christina F. Thobakgale, Mary van der Stok, Shabashini Reddy, Zenele Mncube, Fundisiwe Chonco, Bruce D. Walker, Marcus Altfeld, Philip J. R. Goulder, and Thumbi Ndung'u. Immunodominant HIV-1-Specific HLA-B- and HLA-C-Restricted CD8+ T Cells Do Not Differ in Polyfunctionality. Virology, 405(2):483-491, 30 Sep 2010. PubMed ID: 20638093. Show all entries for this paper.

Displaying record number 53638

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	p24(308-316)
Epitope	`QATQDVKNW`	Epitope Alignment
Epitope Name	QW9
Subtype	C
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Country	Ethiopia
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	immunodominance, escape, variant cross-reactivity

Notes

Epitope sequence variation and CD8 T-cell responses were analyzed in C subtype infected HLA-B57-positive individuals from Ethiopia. KF11 was the immunodominant response.
QATQDVKNW had a single variant, D5E (QATQEVKNW) in 1 subject; there was no apparent immune selection in this epitope. The QW9 peptide was tested in 2 B57-positive subjects; neither responded.

References

Currier2005 Jeffrey R. Currier, Matthew E. Harris, Josephine H. Cox, Francine E. McCutchan, Deborah L. Birx, Shlomo Maayan, and Guido Ferrari. Immunodominance and Cross-Reactivity of B5703-Restricted CD8 T Lymphocytes from HIV Type 1 Subtype C-Infected Ethiopians. AIDS Res. Hum. Retroviruses, 21(3):239-245, Mar 2005. PubMed ID: 15795531. Show all entries for this paper.

Displaying record number 58690

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	Gag(308-316)
Epitope	`QATQDVKNW`	Epitope Alignment
		Show epitope variants
Epitope Name	QW9
Subtype	C
Species (MHC/HLA)	human(B57:02, B57:03, B*58:01)
Immunogen	HIV-1 infection
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	HLA associated polymorphism

Notes

1,010-HIV C clade-chronically infected subjects were tested in order to distinguish levels of immune control by related but different HLA-B*57/58. B*57 micropolymorphisms (B*5703 and B*5702) as well as B*5801 have differing CTL specificity and also present different p24 Gag epitopes. This results in different immune selection pressures on the HIV-C virus.
Though all three studied HLA alleles, B*5801, B*5702 and B*5703 are significantly associated with lower viral-load (VL) set points, HLA-B*5703, followed closely by B*5702 is the most potent controller with lowest VL and HLA-B*5702, followed by B*5703 and then B*5801 are associated with highest CD4 counts.
By using 410 overlapping 18-mers that span the HIV-C proteome in EliSpot assays, 17 epitopes were identified that are presented by one of HLAs-B*5801/5702/5703, 13 of them novel.
Epitope QW9, QATQDVKNW, was previously known to be restricted by HLA-B*5703. Here it is shown to be restricted, though rarely, by HLAs B*5702 and B*5801 as well. QW9 was recognized by ˜50% of B*5702 and B*5801 subjects and by >20% of B*5703 subjects. QW9 was confirmed to be optimal by peptide truncation using B*5801-restricted CTL from chronically infected subject N067.
The binding affinity of QW9 is greatest to B*5702, followed by B*5703 and B*5801. HLA-peptide stability of QW9 to HLA-B*5702 is less than to HLAs B*5703 and B*5801.
There were very few escapes detected in HLA-B*5801 positive subjects only.

References

Kloverpris2012 Henrik N. Kloverpris, Anette Stryhn, Mikkel Harndahl, Mary van der Stok, Rebecca P. Payne, Philippa C. Matthews, Fabian Chen, Lynn Riddell, Bruce D. Walker, Thumbi Ndung'u, Søren Buus, and Philip Goulder. HLA-B*57 Micropolymorphism Shapes HLA Allele-Specific Epitope Immunogenicity, Selection Pressure, and HIV Immune Control. J. Virol., 86(2):919-929, Jan 2012. PubMed ID: 22090105. Show all entries for this paper.

Displaying record number 61216

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	Gag
Epitope	`QATQDVKNW`	Epitope Alignment
		Show epitope variants
Epitope Name	QW9
Subtype	B
Species (MHC/HLA)	human(B57:02, B57:03, B*58:01)
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 QATQDVKNW is restricted by strongly protective alleles. Escapes are found at A309S and T310S.

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 61677

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	Gag(308-316)
Epitope	`QATQDVKNW`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag-QW9
Subtype	C
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, United Kingdom, Zimbabwe
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA associated polymorphism

Notes

Since CTL targeting frequency and risk of immune escape are dependent on the genetic context in which the epitope is presented, systematic computational analyses of differential patterns of immune escape across all optimally defined epitopes in Gag, Pol and Nef in 2,126 HIV-1 clade C-infected adults were performed. 301 polymorphisms were identified in 90 epitopes associated with HLA alleles belonging to shared supertypes, while 37/38 eptiopes restricted by more than one HLA allele represented 278 instances of differential polymorphic escape. 66-97% of these polymorphisms tested were the result of unique HLA-specific polymorphisms rather than differential epitope targeting rates. Total number of polymorphisms also strongly correlated with average VL (viral load).
Differential escape among protective B58-supertype alleles were studied. Several polymorphisms of Gag optimal epitope, QW9, QATQDVKNW, were seen. QsTQDVKNW with S at P2i s associated HLA-B*5801. Escape QAsQDVKNW at P3 was more significantly associated with B*5801 than B*5702 or B*5703. WT A at P2 and T at P3 are associated with B*5801, position P3, more significantly than either B*5702 or B*5703.

References

Carlson2012 Jonathan M. Carlson, Jennifer Listgarten, Nico Pfeifer, Vincent Tan, Carl Kadie, Bruce D. Walker, Thumbi Ndung'u, Roger Shapiro, John Frater, Zabrina L. Brumme, Philip J. R. Goulder, and David Heckerman. Widespread Impact of HLA Restriction on Immune Control and Escape Pathways of HIV-1. J. Virol., 86(9):5230-5243, May 2012. PubMed ID: 22379086. Show all entries for this paper.

Displaying record number 56475

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	p24
Epitope	`QATQDVKNW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Country	South Africa
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).
QATQDVKNW is a previously described HLA-B*5801-restricted epitope (part of Gag reacting peptide FFKTLRAEQAtQDVKNWMTDT) that contains a B*5801-associated reversion at residue T (QAtQDVKNW).

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 56596

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	p24(308-316)
Epitope	`QATQDVKNW`	Epitope Alignment
Epitope Name	QW9
Subtype	C
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Country	South Africa, Zambia
Experimental methods
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

A cohort of clade C-infected Zambian HIV-1 transmission pairs was studied. Accumulation in the donor of HLA-B restricted mutations in Gag, but not in Nef resulted in a reduced viral load in a recipient upon transmission.
20 mutations in Gag and 11 mutations in Nef, within or flanking CTL epitopes, were considered based on data from a Clade C South African cohort. HLA-B*5801-restricted QATQDVKNW (QW9) was associated with polymorphism at QA(T)QDVKNW.

References

Goepfert2008 Paul A. Goepfert, Wendy Lumm, Paul Farmer, Philippa Matthews, Andrew Prendergast, Jonathan M. Carlson, Cynthia A. Derdeyn, Jianming Tang, Richard A. Kaslow, Anju Bansal, Karina Yusim, David Heckerman, Joseph Mulenga, Susan Allen, Philip J. R. Goulder, and Eric Hunter. Transmission of HIV-1 Gag Immune Escape Mutations Is Associated with Reduced Viral Load in Linked Recipients. J. Exp. Med., 205(5):1009-1017, 12 May 2008. PubMed ID: 18426987. Show all entries for this paper.

Displaying record number 53337

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HXB2 Location	Gag(308-316) p24(176-184) DNA(1711..1737)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`QATQDVKNW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*58:01)
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.