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Differential immunodominance hierarchy OF CD8+ T cell responses in HLA-B*27:05 AND B*27:02-mediated control of HIV-1 infection

Adland, E., Hill, M., Lavandier, N., Csala, A., Edwards, A., Chen, F., Radkowski, M., Kowalska, J.D., Paraskevis, D., Hatzakis, A., Valenzuela-Ponce, H., Pfafferott, K., Williams, I., Pellegrino, P., Borrow, P., Mori, M., Rockstroh, J., Prado, J.G., Mothe, B., Dalmau, J., Martinez-Picado, J., Tudor-Williams, G., Frater, J., Stryhn, A., Buus, S., Reyes Teran, G., Mallal, S., John, M., Buchbinder, S., Kirk, G., Martin, J., Michael, N., Fellay, J., Deeks, S., Walker, B.ORCID: 0000-0002-8506-6740, Avila-Rios, S., Cole, D., Brander, C., Carrington, M. and Goulder, P. (2017) Differential immunodominance hierarchy OF CD8+ T cell responses in HLA-B*27:05 AND B*27:02-mediated control of HIV-1 infection. Journal of Virology, 82 (4). e01685-e016817.

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Abstract

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: American Society for Microbiology
Copyright: © 2018 Adland et al.
United Nations SDGs: Goal 3: Good Health and Well-Being
URI: http://researchrepository.murdoch.edu.au/id/eprint/40190
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