Search CTL/CD8+ T-Cell Epitope Database

Found 5 matching records:

Displaying record number 56504

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase
Epitope	`SAAVKAACWW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*58:01)
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).
SAAVKAACWW is a previously described HLA-B*5801-restricted epitope (part of Pol(Integrase) reacting peptide HTDNGSNFTSaAVKAACWWAG) that contains a B*5801-associated reversion at residue A (SaAVKAACWW).

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 57896

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase
Epitope	`SAAVKAACWW`	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	rate of progression, acute/early infection

Notes

HLA-B*5801 is associated with slow progression. Six B*5801-positive subtype C-infected subjects were followed for up to 31 months from infection. CTL responses during acute infection predominantly targeted the TW10 and KF9 epitopes. Transmitted escape and compensatory mutations appeared to limit the protective effect of the B*5801 allele.
In EliSpot assays of overlapping peptides across the entire proteome, 1/6 patients targeted a peptide containing this epitope; a single-peptide response was not confirmed.

References

Chopera2011 D. R. Chopera, M. Mlotshwa, Z. Woodman, K. Mlisana, D. de Assis Rosa, D. P. Martin, S. Abdool Karim, C. M. Gray, C. Williamson, and CAPRISA 002 Study Team. Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals. J. Virol., 85(14):7070-7080, Jul 2011. PubMed ID: 21613398. Show all entries for this paper.

Displaying record number 57904

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase
Epitope	`SAAVKAACWW`	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	rate of progression, acute/early infection

Notes

HLA-B*5801 is associated with slow progression. Six B*5801-positive subtype C-infected subjects were followed for up to 31 months from infection. CTL responses during acute infection predominantly targeted the TW10 and KF9 epitopes. Transmitted escape and compensatory mutations appeared to limit the protective effect of the B*5801 allele.
In EliSpot assays of overlapping peptides across the entire proteome, 1/6 patients targeted a peptide containing this epitope; a single-peptide response was not confirmed.

References

Displaying record number 61626

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase
Epitope	`SAAVKAACWW`	Epitope Alignment
Epitope Name	B*57-SW10
Subtype	C
Species (MHC/HLA)	human(B*58:01)
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 Int epitope, SAAVKAACWW (SW10) was targeted by subjects SK-187, SK-242 (or SK-024) and SK-188 (or SK-079), failing VCs, only before loss of viremic control (EliSpots = 180, 500, and 380 sfu/10⁶). For VCs, SW10 was targeted by subject -SK-282, before and after loss of viremic control (EliSpots = 360/436 sfu/10⁶).

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 62883

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HXB2 Location	Pol(838-847) Integrase(123-132)	Pol Epitope Map
Author Location	Integrase(123-132)
Epitope	`SAAVKAACWW`	Epitope Alignment
		Show epitope variants
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 <i>in vitro</i> 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 mutations S119T, S119R or Q136K did not mediate a significant reduction in RC while the introduction of S119P did not produce detectable cultured virus and the introduction of A124N mediated the largest assessed RC reduction of ˜23%.
Relative to subtype B wild-type NL4-3, the introduction of mutations S119T or S119P did not mediate a significant reduction in RC while the introduction of S119R did not produce detectable cultured virus, suggesting subtype-specific functional consequences of S119P/R mutants.
A124N is located within best-defined integrase epitope SW10 (SttVKAACWW in NL4-3 and known to bind to B*57, but SAAVKAACWW in SK-278) while residues 119 and 136 are located 4 AA upstream (in epitope HTDNGSNF) and 4 AA downstream (in epitope IQQEFGIPY), respectively, from SW10.

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.