Persistent survival of prevalent clonotypes within an immunodominant HIV gag-specific CD8+ T cell response

van Bockel, David J., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Munier, Mee Ling, Venturi, Vanessa, Asher, Tedi E., Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, Greenaway, Hui Yee, Zaunders, John, Douek, Daniel C., Cooper, David A., Davenport, Miles P. and Kelleher, Anthony D. 2010. Persistent survival of prevalent clonotypes within an immunodominant HIV gag-specific CD8+ T cell response. The Journal of Immunology 186 (1) , pp. 359-371. 10.4049/jimmunol.1001807

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Abstract

CD8+ T cells play a significant role in the control of HIV replication, yet the associated qualitative and quantitative factors that determine the outcome of infection remain obscure. In this study, we examined Ag-specific CD8+ TCR repertoires longitudinally in a cohort of HLA-B*2705+ long-term nonprogressors with chronic HIV-1 infection using a combination of molecular clonotype analysis and polychromatic flow cytometry. In each case, CD8+ T cell populations specific for the immunodominant p24 Gag epitope KRWIILGLNK (KK10; residues 263–272) and naturally occurring variants thereof, restricted by HLA-B*2705, were studied at multiple time points; in addition, comparative data were collected for CD8+ T cell populations specific for the CMV pp65 epitope NLVPMVATV (NV9; residues 495–503), restricted by HLA-A*0201. Dominant KK10-specific clonotypes persisted for several years and exhibited greater stability than their contemporaneous NV9-specific counterparts. Furthermore, these dominant KK10-specific clonotypes exhibited cross-reactivity with antigenic variants and expressed significantly higher levels of CD127 (IL-7Rα) and Bcl-2. Of note, we also found evidence that promiscuous TCR α-chain pairing associated with alterations in fine specificity for KK10 variants could contribute to TCR β-chain prevalence. Taken together, these data suggest that an antiapoptotic phenotype and the ability to cross-recognize variant epitopes contribute to clonotype longevity and selection within the peripheral memory T cell pool in the presence of persistent infection with a genetically unstable virus.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Date of Acceptance:	4 October 2010
Last Modified:	20 Oct 2022 08:51
URI:	https://orca.cardiff.ac.uk/id/eprint/29841

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