title: The molecular basis of TCR germline bias for MHC is surprisingly simple.
abstract: The elusive etiology of germline bias of the T cell receptor (TCR) for major histocompatibility complex (MHC) has been clarified by recent 'proof-of-concept' structural results demonstrating the conservation of specific TCR-MHC interfacial contacts in complexes bearing common variable segments and MHC allotypes. We suggest that each TCR variable-region gene product engages each type of MHC through a 'menu' of structurally coded recognition motifs that have arisen through coevolution. The requirement for MHC-restricted T cell recognition during thymic selection and peripheral surveillance has necessitated the existence of such a coded recognition system. Given these findings, a reconsideration of the TCR-peptide-MHC structural database shows that not only have the answers been there all along but also they were predictable by the first principles of physical chemistry.
authors.affiliation: Department of Molecular & Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA. kcgarcia@stanford.edu
authors.forename: K Christopher
authors.initials: KC
authors.lastname: Garcia
authors.forename: Jarrett J
authors.initials: JJ
authors.lastname: Adams
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Ely
mesh_terms: D000818:Animals; D019672:Genes, T-Cell Receptor; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D020836:Protein Structure, Quaternary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell