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Reversed T cell receptor docking on a major histocompatibility class I complex limits involvement in the immune response

Gras, Stephanie, Chadderton, Jesseka, Del Campo, Claudia M., Farenc, Carine, Wiede, Florian, Josephs, Tracy M., Sng, Xavier Y. X., Mirams, Michiko, Watson, Katherine A., Tiganis, Tony, Quinn, Kylie M., Rossjohn, Jamie and La Gruta, Nicole L. 2016. Reversed T cell receptor docking on a major histocompatibility class I complex limits involvement in the immune response. Immunity 45 (4) , pp. 749-760. 10.1016/j.immuni.2016.09.007

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Abstract

The anti-viral T cell response is drawn from the naive T cell repertoire. During influenza infection, the CD8+ T cell response to an H-2Db-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of T cells bearing TRBV13+ T cell receptors (TCRs) and avoidance of TRBV17+ T cells, despite the latter dominating the naive precursor repertoire. We found two TRBV17+ TCRs that bound H-2Db-NP366 with a 180° reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 β-chain dominated the interaction and, whereas the complementarity determining region-3 (CDR3) loops exclusively mediated contacts with the MHC-I, peptide specificity was attributable to germline-encoded recognition. Nevertheless, the TRBV17+ TCR exhibited moderate affinity toward H-2Db-NP366 and was capable of signal transduction. Thus, the naive CD8+ T cell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 1074-7613
Date of First Compliant Deposit: 27 July 2017
Date of Acceptance: 6 August 2016
Last Modified: 23 May 2018 00:41
URI: http://orca-mwe.cf.ac.uk/id/eprint/100009

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