title: Determination of the peptide binding motif and high-affinity ligands for HLA-DQ4 using synthetic peptide libraries.
abstract: 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.
authors.affiliation: University Children's Hospital, Tuebingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Volz
authors.forename: Gerold
authors.initials: G
authors.lastname: Schwarz
authors.forename: Burkhard
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: Carsten P
authors.initials: CP
authors.lastname: Schepp
authors.forename: Markus
authors.initials: M
authors.lastname: Haug
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: Günther E
authors.initials: GE
authors.lastname: Dannecker
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D001171:Arthritis, Juvenile / Q000276:immunology* / Q000473:pathology; D002461:Cell Line, Transformed; D006683:HLA-DQ Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology
chemical_list: D006683:HLA-DQ Antigens; C060029:HLA-DQ4 antigen; C069546:HLA-DQ7 antigen; D008024:Ligands; D019151:Peptide Library; D010455:Peptides