Interaction codons mediating germline specificity of the T cell receptor (TCR) for MHC. (a) This panel shows the wide range of TCR docking angles on MHC seen from an overlap for ~40 different class I TCR–MHC complex crystal structures. Conserved interactions that might denote germline contacts have not been evident from this type of analysis. (b) Focused structural studies of Vβ8.2 containing TCRs recognizing similar type of MHC (class II I-A allotypes) reveal a highly convergent mode of germline contact between the TCR CDR1β and CDR2β with the MHC, which we refer to as an interaction codon. The inset shows the amino acids involved in this contact, and the degree of superposition, and also wobble, in the manner by which approximately 10 Vβ8.2 TCRs engage with I-A MHC. (c) Another germline codon, involving a TCR Vα3 and class I MHC H-2Ld also indicates a close structural superposition.