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.