Authors:
Kristin Ladell, Masao Hashimoto, Maria Candela Iglesias, Pascal G. Wilmann, James E. McLaren, Stéphanie Gras, Takayuki Chikata, Nozomi Kuse, Solène Fastenackels, Emma Gostick, John S. Bridgeman, Vanessa Venturi, Zaïna Aït Arkoub, Henri Agut, David J. van Bockel, Jorge R. Almeida, Daniel C. Douek, Laurence Meyer, Alain Venet, Masafumi Takiguchi, Jamie Rossjohn, David A. Price, & Victor Appay
Summary:
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)-B2705. 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-B2705+ 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.
Source:
Immunity; Vol. 38, Issue 3, 425-436 (03/21/13)