Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity.

摘要: Abstract T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features antigen that necessary for the cell's diverse functional repertoire. In crystal structure between an autoreactive, EAE clone 172.10 myelin basic protein (1–11) presented by class II I-A u , is dominated Vβ domain TCR, which interacts α chain in a manner suggestive germline-encoded TCR/MHC "anchor point." Strikingly, there few specific contacts TCR CDR3 loops MBP peptide. We also find over 1,000,000 peptides derived from combinatorial libraries can activate 172.10, yet strongly prefers native contact residues. suggest while scanning pMHC may be degenerate due to germline bias MHC, structurally distinct agonist not indicative promiscuity, but rather highly alternative solutions engagement.