Differential peptide binding motif for three juvenile arthritis associated HLA-DQ molecules.

OBJECTIVE In the oligoarticular subgroup of juvenile idiopathic arthritis, a strong association has been found with the expression of human leukocyte antigen class II molecules HLA-DQA1 *0401-DQB1*0402 and DQA1*0501-DQB1*0301, whereas DQA1*0501-DQB1*0201 is neutral and DQA1 *0201-DQB1*0201 protective. A presentation of different peptides by these DQ alleles would support their role in the disease process. METHODS Using a synthetic nonapeptide library, a peptide binding motif was determined for the associated DQA1*0501-DQB1*0301 molecule and compared to the neutral and the protective DQ molecules. RESULTS A differential motif for the three molecules could be deduced, suggesting that peptides preferentially binding to the associated vs. the neutral/protective DQ-molecules are mutually exclusive. CONCLUSION These results imply a role for differential peptide presentation in the pathogenesis of oligoarthritic JIA. The search for peptides initiating the disease process might be facilitated which could then lead to therapeutical interventions.