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Skip Navigation LinksHome > July 17, 2013 - Volume 27 - Issue 11 > HLA-A*68: 02-restricted Gag-specific cytotoxic T lymphocyte...
AIDS:
doi: 10.1097/QAD.0b013e32836146cd
Basic Science

HLA-A*68: 02-restricted Gag-specific cytotoxic T lymphocyte responses can drive selection pressure on HIV but are subdominant and ineffective

Kløverpris, Henrik N.a,b,h; Stryhn, Anetteb; Harndahl, Mikkelb; Carlson, Jonathan M.g; Leslie, Alasdair J.h; Chen, Fabiane; Riddell, Lynnf; Mulenga, Josephi; Walker, Bruce D.c,d; Ndung’u, Thumbic; Buus, Sørenb; Goulder, Philipa,c

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Abstract

Background: Human leukocyte allele (HLA) class I polymorphism has the greatest impact of human genetic variation on viral load set point. A substantial part of this effect is due to the action of HLA-B and HLA-C alleles. With few exceptions the role of HLA-A molecules in immune control of HIV is unclear.

Methods: We here study HLA-A*68:02, one of the most highly prevalent HLA-A alleles in C-clade infected sub-Saharan African populations, and one that plays a prominent role in the HIV-specific CD8+ T-cell responses made against the virus.

Results: We define eight epitopes restricted by this allele and propose the peptide binding motif for HLA-A*68:02. Although one of these epitopes almost exactly overlaps an HLA-B*57-restricted epitope in Gag linked with immune control of HIV, this HLA-A*68:02-restricted Gag-TA10 response imposed only weak selection pressure on the virus and was not associated with significantly lower viral setpoint. The only HLA-A*68:02-restricted responses imposing strong selection pressure on HIV were in the flanking regions of Pol-EA8 and Pol-EA11 and within the Vpr-EV10 epitope (P = 8 × 10−8). However, targeting of this latter epitope was associated with significantly higher viral loads (P = 0.003), suggesting lack of efficacy.

Conclusion: This study is consistent with previous data showing that HLA-A-restricted Gag-specific responses can impose selection pressure on HIV. In the case of HLA-A*68:02 the Gag response is subdominant, and apparently has little impact in natural infection. However, these data suggest the potential for high frequency vaccine-induced Gag responses restricted by this allele to have significant antiviral efficacy in vaccine recipients.

© 2013 Lippincott Williams & Wilkins, Inc.

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