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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). 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.

Original publication

DOI

10.1097/QAD.0b013e32836146cd

Type

Journal article

Journal

AIDS

Publication Date

17/07/2013

Volume

27

Pages

1717 - 1723

Keywords

Africa South of the Sahara, CD8-Positive T-Lymphocytes, Epitopes, HIV, HLA-A Antigens, Humans, Nuclear Pore Complex Proteins, Selection, Genetic, T-Lymphocytes, Cytotoxic, gag Gene Products, Human Immunodeficiency Virus