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

Ladell, Kristin Ingrid, Hashimoto, Masao, Iglesias, Maria Candela, Wilmann, Pascal G., McLaren, James Edward, Gras, Stéphanie, Chikata, Takayuki, Kuse, Nozomi, Fastenackels, Solène, Gostick, Emma, Bridgeman, John S., Venturi, Vanessa, Arkoub, Zaïna Aït, Agut, Henri, van Bockel, David J., Almeida, Jorge R., Douek, Daniel C., Meyer, Laurence, Venet, Alain, Takiguchi, Masafumi, Rossjohn, Jamie, Price, David and Appay, Victor 2013. A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells. Immunity 38 (3) , pp. 425-436. 10.1016/j.immuni.2012.11.021

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology Q Science > QR Microbiology > QR355 Virology R Medicine > RM Therapeutics. Pharmacology
Publisher:	Cell Press
ISSN:	1074-7613
Last Modified:	14 Nov 2017 21:01
URI:	http://orca-mwe.cf.ac.uk/id/eprint/48536

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