最新immunity文章，CTL如何控制HIV逃逸

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A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8+ T Cells


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. New T cell clonotypes are recruited to counter TCR-accessible HIV mutations These T cells express TCRs that crossrecognize wild-type and mutant epitopes Crossreactive CD8+ T cells underpin anti-HIV efficacy in HLA-B∗27+ patients T cell efficacy ultimately drives escape mutations that impact antigen presentation.

http://www.cell.com/immunity/abstract/S1074-7613(13)00106-4