TCR β-Chain sharing in human CD8+ T cell responses to cytomegalovirus and EBV

Venturi, Vanessa, Chin, Hui Yee, Tedi, E. Asher, Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, Scheinberg, Phillip, Bornstein, Ethan, van Bockel, David, Kelleher, Anthony D., Douek, Daniel C., Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737 and Davenport, Miles P. 2008. TCR β-Chain sharing in human CD8+ T cell responses to cytomegalovirus and EBV. Journal of Immunology 181 (11) , pp. 7853-7862. 10.4049/​jimmunol.181.11.7853

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Abstract

The CD8+ TCR repertoires specific for many immunogenic epitopes of CMV and EBV are dominated by a few TCR clonotypes and involve public TCRs that are shared between many MHC-matched individuals. In previous studies, we demonstrated that the observed sharing of epitope-specific TCRβ chains between individuals is strongly associated with TCRβ production frequency, and that a process of convergent recombination facilitates the more efficient production of some TCRβ sequences. In this study, we analyzed a total of 2836 TCRβ sequences from 23 CMV-infected and 10 EBV-infected individuals to investigate the factors that influence the sharing of TCRβ sequences in the CD8+ T cell responses to two immunodominant HLA-A*0201-restricted epitopes from these viruses. The most shared TCRβ amino acid sequences were found to have two features that indicate efficient TCRβ production, as follows: 1) they required fewer nucleotide additions, and 2) they were encoded by a greater variety of nucleotide sequences. We used simulations of random V(D)J recombination to demonstrate that the in silico TCRβ production frequency was predictive of the extent to which both TCRβ nucleotide and amino acid sequences were shared in vivo. These results suggest that TCRβ production frequency plays an important role in the interindividual sharing of TCRβ sequences within CD8+ T cell responses specific for CMV and EBV.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Association of Immunologists
ISSN:	1550-6606
Last Modified:	18 Oct 2022 14:29
URI:	https://orca.cardiff.ac.uk/id/eprint/17732

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