National Center for
5SWZ: Crystal Structure Of Np1-b17 Tcr-h2db-np Complex
Reversed T Cell Receptor Docking on a Major Histocompatibility Class I Complex Limits Involvement in the Immune Response
Immunity (2016) 45 p.749-760
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 degrees reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 beta-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.