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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; La Gruta, Nicole L.
Immunity (Cambridge, Mass.), 10/2016, Volume: 45, Issue: 4Journal Article
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. •TCRs found on naive T cells ligate pMHC-I in a 180° reversed orientation•CD8+ T cells expressing “reversed” TCRs contribute minimally to the immune response•Reversed TCR recognition drives limited signal transduction and T cell function•Unconventionally docking TCRs may be prevalent in the naive pool 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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