Negatively charged residues interacting with the p4 pocket confer binding specificity to DRB1*0401

OBJECTIVE: To identify critical residues involved in the binding of a selective peptide to DRB1*0401. METHODS: The binding of peptides to native or site-directed mutant DR molecules was evaluated using enzyme-linked immunosorbent assay and flow cytometry. RESULTS: Amino acid substitutions at DR and peptide residues, which were predicted to contribute to interactions within the DR p4 pocket, had the greatest effects on the specificity of binding. CONCLUSION: Differences in the peptide-binding repertoires of DR molecules may contribute to associations with autoimmune diseases.