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

DSpace/Manakin Repository

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

Citable link to this page

 

 
Title: Nef-Specific CD8+ T Cell Responses Contribute to HIV-1 Immune Control
Author: Adland, Emily; Carlson, Jonathan M.; Paioni, Paolo; Kløverpris, Henrik; Shapiro, Roger; Ogwu, Anthony; Riddell, Lynn; Luzzi, Graz; Chen, Fabian; Balachandran, Thambiah; Heckerman, David; Stryhn, Anette; Edwards, Anne; Ndung’u, Thumbi; Walker, Bruce D.; Buus, Søren; Goulder, Philip; Matthews, Philippa C.

Note: Order does not necessarily reflect citation order of authors.

Citation: 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.
Full Text & Related Files:
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.
Published Version: doi:10.1371/journal.pone.0073117
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759414/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11877010
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters