Nef-Specific CD8+ T Cell Responses Contribute to HIV-1 Immune Control

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Author
Adland, Emily
Carlson, Jonathan M.
Paioni, Paolo
Kløverpris, Henrik
Ogwu, Anthony
Riddell, Lynn
Luzzi, Graz
Chen, Fabian
Balachandran, Thambiah
Heckerman, David
Stryhn, Anette
Edwards, Anne
Ndung’u, Thumbi
Buus, Søren
Goulder, Philip
Matthews, Philippa C.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0073117Metadata
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Adland, E., J. M. Carlson, P. Paioni, H. Kløverpris, R. Shapiro, A. Ogwu, L. Riddell, et al. 2013. “Nef-Specific CD8+ T Cell Responses Contribute to HIV-1 Immune Control.” PLoS ONE 8 (9): e73117. doi:10.1371/journal.pone.0073117. http://dx.doi.org/10.1371/journal.pone.0073117.Abstract
Recent studies in the SIV-macaque model of HIV infection suggest that Nef-specific CD8+ T-cell responses may mediate highly effective immune control of viraemia. In HIV infection Nef recognition dominates in acute infection, but in large cohort studies of chronically infected subjects, breadth of T cell responses to Nef has not been correlated with significant viraemic control. Improved disease outcomes have instead been associated with targeting Gag and, in some cases, Pol. However analyses of the breadth of Nef-specific T cell responses have been confounded by the extreme immunogenicity and multiple epitope overlap within the central regions of Nef, making discrimination of distinct responses impossible via IFN-gamma ELISPOT assays. Thus an alternative approach to assess Nef as an immune target is needed. Here, we show in a cohort of >700 individuals with chronic C-clade infection that >50% of HLA-B-selected polymorphisms within Nef are associated with a predicted fitness cost to the virus, and that HLA-B alleles that successfully drive selection within Nef are those linked with lower viral loads. Furthermore, the specific CD8+ T cell epitopes that are restricted by protective HLA Class I alleles correspond substantially to effective SIV-specific epitopes in Nef. Distinguishing such individual HIV-specific responses within Nef requires specific peptide-MHC I tetramers. Overall, these data suggest that CD8+ T cell targeting of certain specific Nef epitopes contributes to HIV suppression. These data suggest that a re-evaluation of the potential use of Nef in HIV T-cell vaccine candidates would be justified.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759414/pdf/Terms of Use
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