Escape from highly effective public CD8+ T-cell clonotypes by HIV

Maria Iglesias, Jorge Almeida, Solene Fastenackels, David van Bockel, Masao Hashimoto, Vanessa Venturi, Emma Gostick, Alejandra Urrutia, Linda Wooldridge, Mathew Clement, Stephanie Gras, Pascal Wilmann, Brigitte Autran, Arnaud Moris, Jamie Rossjohn, Miles Davenport, Masafumi Takiguchi, Christian Brander, Daniel Douek, Anthony D KelleherDavid Price, Victor Appay

Research output: Contribution to journalArticleResearchpeer-review

79 Citations (Scopus)

Abstract

Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These public clonotypes exhibit high levels of TCR avidity and antigen sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L(268)M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8(+) T-cell response against HIV.
Original languageEnglish
Pages (from-to)2138 - 2149
Number of pages12
JournalBlood
Volume118
Issue number8
DOIs
Publication statusPublished - 2011

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