The role of I-Ag7 beta chain in peptide binding and antigen recognition by T cells.

We examine here how the beta chain of the class II MHC molecule I-Ag7 influences T cell recognition. Three sets of T cell clones were identified. The first set recognizes peptides bound to I-Ag7, I-Ad and I-Ag7 mutant in which the allele-specific residues His and Ser at position 56 and 57 were changed to the Pro at residue 56 and to non-polymorphic Asp at residue 57. The second set responds to the antigen presented only by I-Ag7 and does not recognize the peptides bound to the other class II molecules. The third set is also specific for I-Ag7 as a result of the poor binding of the peptide to I-Ad and the mutant I-Ag7. These results indicate that positions 56 and 57 of the I-Ag7 class II MHC beta chain play a role in both T cell recognition of the MHC-peptide complex and peptide binding to MHC. These two different functions may be involved in I-Ag7-restricted beta cell antigen recognition by diabetogenic T cell clones.