ab21220

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

J. Ihle¹, B. Fleckenstein², C. Terreaux³, H. Beck⁴, E.D. Albert⁵, G.E. Dannecker¹

¹University Children's Hospital, Eberhard Karls University, Tübingen, Germany; ²Institute for Organic Chemistry, Eberhard Karls University, Tübingen, Germany; ³Institut de Pharmacognosie et Phytochimie BEP, Université de Lausanne, Switzerland; ⁴Institute for Biochemistry, Eberhard Karls University, Tübingen, Germany; ⁵Institute for Immunogenetics, Ludwig-Maximilians University, Munich, Germany

ABSTRACT
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.

Key words
HLA-DQ, juvenile idiopathic arthritis, peptide binding motif, peptide library.

This work was supported by a grant from the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 510.
Please address correspondence to: Johannes Ihle, MD, Charité Virchow-Klinikum, Kinderklinik, SPZ Rheumatologie, Augustenburger Platz no. 1, 13353 Berlin, Germany.
E-mail: johannes.ihle@web.de