T cell receptor interaction with peptide/major histocompatibility complex (MHC) and superantigen/MHC ligands is dominated by antigen.

• DOI: 10.1084/jem.178.2.713
• Publication Date: 2004-06-24T07:56:10Z
• Authors: E W Ehrich; B Devaux; E P Rock; J L Jorgensen; M M Davis; Y H Chien
• Keywords: MHC restriction; Superantigen; Antigen processing

While recent evidence strongly suggests that the third complementarity determining regions (CDR3s) of T cell receptors (TCRs) directly contact antigenic peptides bound to major histocompatibility complex (MHC) molecules, nature other TCR contact(s) is less clear. Here we probe extent which different antigens can affect this interaction by comparing responses cells bearing structurally related TCRs cytochrome c and staphylococcal enterotoxin A (SEA) presented 13 mutant antigen-presenting (APC) lines. Each APC expresses a class II MHC molecule (I-Ek) with single substitution an amino acid residue predicted be located on alpha helices point "up" towards TCR. We find very limited changes (even acid) in either CDR3 loop or peptide have profound effect relatively distant TCR/MHC interactions. The these effects as great observed between entirely recognizing peptides. also superantigen presentation entails distinct mode compared presentation. These data suggest contacts made variety ways same MHC, final configuration apparently dominated antigen. observations molecular basis for reports analogues superantigens trigger pathways activation.