5SWZ

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

(2016) Immunity 45: 749-760

• PubMed: 27717799 Search on PubMed
• DOI: https://doi.org/10.1016/j.immuni.2016.09.007
• Primary Citation of Related Structures:  
  5SWS, 5SWZ


• PubMed 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-2D ^b -restricted nucleoprotein epitope (NP ₃₆₆ ) 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 -NP ₃₆₆ 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 -NP ₃₆₆ 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.

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Organizational Affiliation: 

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.