Abstract
The anti-viral Tcell response is drawn from the naive Tcell repertoire. During influenza infection, the CD8+ Tcell response to an H-2Db-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of Tcells bearing TRBV13+ Tcell receptors (TCRs) and avoidance of TRBV17+ Tcells, 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+ Tcell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.
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