HLA-A*68:02-restricted Gag-specific cytotoxic T lymphocyte responses can drive selection pressure on HIV but are subdominant and ineffective
In: AIDS (London), Jg. 27 (2013), Heft 11, S. 1717-1723
Online
academicJournal
- print, 18 ref
Zugriff:
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.
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HLA-A*68:02-restricted Gag-specific cytotoxic T lymphocyte responses can drive selection pressure on HIV but are subdominant and ineffective
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Autor/in / Beteiligte Person: | KLØVERPRIS, Henrik N ; STRYHN, Anette ; BUUS, Søren ; GOULDER, Philip ; HARNDAHL, Mikkel ; CARLSON, Jonathan M ; LESLIE, Alasdair J ; CHEN, Fabian ; RIDDELL, Lynn ; MULENGA, Joseph ; WALKER, Bruce D ; NDUNG'U, Thumbi |
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Zeitschrift: | AIDS (London), Jg. 27 (2013), Heft 11, S. 1717-1723 |
Veröffentlichung: | Hagerstown, MD: Lippincott Williams & Wilkins, 2013 |
Medientyp: | academicJournal |
Umfang: | print, 18 ref |
ISSN: | 0269-9370 (print) |
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