Reversed T Cell Receptor Docking on a Major Histocompatibility Class I Complex Limits Involvement in the Immune Response

Publication date: Available online 4 October 2016
Source:Immunity
Author(s): Stephanie Gras, Jesseka Chadderton, Claudia M. Del Campo, Carine Farenc, Florian Wiede, Tracy M. Josephs, Xavier Y.X. Sng, Michiko Mirams, Katherine A. Watson, Tony Tiganis, Kylie M. Quinn, Jamie Rossjohn, Nicole L. La Gruta
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-2D^b-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-2D^b-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-2D^b-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.

Teaser

Gras et al. show that TCRs from the naive repertoire recognize pMHC-I in a reversed orientation in comparison to the consensus TCR-pMHC-I docking. This reversed docking was associated with poor CD8⁺ T cell responses. Thus, naive T cells may exhibit a range of unconventional TCR-pMHC-I docking modes.


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