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.