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

Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, Hashimoto, Masao, Iglesias, Maria Candela, Wilmann, Pascal G., McLaren, James Edward ORCID: https://orcid.org/0000-0002-7021-5934, 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 ORCID: https://orcid.org/0000-0002-2020-7522, Price, David ORCID: https://orcid.org/0000-0001-9416-2737 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:	Schools > Medicine Research Institutes & Centres > 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:	10 Nov 2022 13:30
URI:	https://orca.cardiff.ac.uk/id/eprint/48536

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