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  ORCID: https://orcid.org/0000-0002-2020-7522 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: | 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: | 25 Nov 2024 23:15 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/100009 |
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