Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'.
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'.
Feng
Dan
D
Howard Hughes Medical Institute, Department of Molecular & Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Bond
Christopher J
CJ
Ely
Lauren K
LK
Maynard
Jennifer
J
Garcia
K Christopher
KC
D000595:Amino Acid Sequence; D000818:Animals; D003460:Crystallization; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics; D020349:Surface Plasmon Resonance
D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta