A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells

Kristin Ladell, Masao Hashimoto, Maria Candela Iglesias, Pascal Georges Wilmann, James E McLaren, Stephanie Gras, Takayuki Chikata, Nozomi Kuse, Solene Fastenackels, Emma Gostick, John S Bridgeman, Vanessa Venturi, Zaina A Arkoub, Henri Agut, David J van Bockel, Jorge R Almeida, Daniel C Douek, Laurence Meyer, Alain Venet, Masafumi TakiguchiJamie Rossjohn, David A Price, Victor Appay

Research output: Contribution to journalArticleResearchpeer-review

101 Citations (Scopus)

Abstract

The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8+ T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK263-272) presented by human leukocyte antigen (HLA)-B *2705. We found that cross-reactive CD8+ T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B *2705+ individuals. A protective CD8+ T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.
Original languageEnglish
Pages (from-to)425 - 436
Number of pages12
JournalImmunity
Volume38
Issue number3
DOIs
Publication statusPublished - 2013

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