Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'

Nat Immunol. 2007 Sep;8(9):975-83. doi: 10.1038/ni1502. Epub 2007 Aug 12.

Abstract

All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable beta-chain 8.2 (V(beta)8.2), each bound to the MHC class II molecule I-A(u), and did energetic mapping of V(alpha) and V(beta) contacts with I-A(u). Together with two previously solved structures of V(beta)8.2-containing TCR-MHC complexes, we found four TCR-I-A complexes with structurally superimposable interactions between the V(beta) loops and the I-A alpha-helix. This examination of a narrow 'slice' of the TCR-MHC repertoire demonstrates what is probably one of many germline-derived TCR-MHC interaction 'codons'.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallization
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Histocompatibility Antigens Class II / chemistry*
  • Major Histocompatibility Complex*
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Quaternary*
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Surface Plasmon Resonance

Substances

  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell, alpha-beta

Associated data

  • PDB/2PXY
  • PDB/2Z31
  • PDB/2Z35