title: Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide.
abstract: T cell receptors (TCRs) bind complexes of cognate major histocompatibility complex (MHC) and peptide at relatively low affinities (1-200 microM). Nevertheless, TCR-MHC-peptide interactions are usually specific for the peptide and the allele encoding the MHC. Here we show that to escape thymocyte negative selection, TCRs must interact with many of the side chains of MHC-peptide complexes as 'hot spots' for TCR binding. Moreover, even when the 'parental' side chain did not contribute binding affinity, some MHC-peptide residues contributed to TCR specificity, as amino acid substitutions substantially reduced binding affinity. The presence of such 'interface-disruptive' side chains helps to explain how TCRs generate specificity at low-affinity interfaces and why TCRs often 'accommodate' a subset of amino acids at a given MHC-peptide position.
authors.affiliation: Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Huseby
authors.forename: Frances
authors.initials: F
authors.lastname: Crawford
authors.forename: Janice
authors.initials: J
authors.lastname: White
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera
chemical_list: D000596:Amino Acids; D006183:H-2 Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell