Determination of the peptide binding motif and high-affinity ligands for HLA-DQ4 using synthetic peptide libraries

• Published in: Human immunology 2004-06, Vol.65 (6), p.594-601
• Main Authors: Volz, Thomas, Schwarz, Gerold, Fleckenstein, Burkhard, Schepp, Carsten P., Haug, Markus, Roth, Johannes, Wiesmüller, Karl-Heinz, Dannecker, Günther E.
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs - immunology; Amino Acid Sequence; Arthritis, Juvenile - immunology; Arthritis, Juvenile - pathology; Cell Line, Transformed; high-affinity ligands; HLA-DQ; HLA-DQ Antigens - immunology; HLA-DQ Antigens - metabolism; Humans; juvenile idiopathic arthritis; Ligands; Molecular Sequence Data; peptide binding motif; Peptide Library; Peptides - chemical synthesis; Peptides - immunology; Peptides - metabolism; Protein Binding - immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2004.02.027

Juvenile idiopathic arthritis (JIA) is considered to be an autoimmune disease. Various human leukocyte antigen (HLA) associations for different subgroups of this heterogeneous disease have been found. For early-onset pauciarticular arthritis (now oligoarthritic JIA), a strong association with the HLA class II haplotype DQA1*0401/DQB1*0402 (DQ4) has been described. We determined the peptide-binding specificities of this HLA-DQ molecule by screening a synthetic acetylated nonapeptide amide library with one defined and eight random sequence positions. A characteristic binding motif could be deduced. By use of these data, we designed defined specific nonapeptides and identified high-affinity ligands binding to HLA-DQ4. The peptide binding motif of HLA-DQ4 is very similar to the motif of HLA-DQ7, also associated with oligoarthritic JIA. It is, however, different from binding motifs of neutral or protective HLA-DQ molecules. Our results further support the idea of differential peptide presentation in the pathogenesis of oligoarthritic JIA.