Analysis of critical residues of HLA-DQ6 molecules in insulin-dependent diabetes mellitus.

Abstract	Among DQ6 molecules, DQA10102-DQB10602 is negatively associated with insulin-dependent diabetes mellitus (IDDM), but DQA10102-DQB10604 shows a neutral to positive association in Swedish children with IDDM. The aim of this study was to identify critical DQB1 residues that may account for the differences in IDDM association observed for these two DQ6 molecules. HLA-DQ genotyping in 425 IDDM patients and 367 matched controls showed DQ6 (B10602) in 1% of patients and 25% of controls (odds ratio (OR) 0.02). DQ6 (B10604) alone was neutral (9% of patients and 10% of controls) but in combination with DQ8, was positively associated (5% of patients, 1% of controls, OR 9.49). In both these DQ6 molecules the alpha-chain is the same but the beta-chain differs at positions 9, 30, 57, 70, 86 and 87. DQB10602 has F9, Y30, D57, G70, A86 and F87, whereas DQB10604 has Y9, H30, V57, R70, G86 and Y87. Three-dimensional models of the two DQ6 molecules, based on crystal coordinates of the homologous DR1 molecule, suggest that residue 57 beta will likely play a critical role in peptide-binding selectivity, whereas residue 70 beta is probably is major contact site for the T-cell receptor. The effects of these specific polymorphic substitutions in DQ molecules on peptide binding and T-cell receptor recognition may be significant in IDDM susceptibility.
Authors	C B Sanjeevi, C DeWeese, M Landin-Olsson, I Kockum, G Dahlquist, A Lernmark, T P Lybrand
Journal	Tissue antigens (Tissue Antigens) Vol. 50 Issue 1 Pg. 61-5 (Jul 1997) ISSN: 0001-2815 [Print] England
PMID	9243758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Autoantibodies HLA-DQ Antigens HLA-DQ alpha-Chains HLA-DQ6 antigen HLA-DQA1 antigen
Topics	Adolescent Autoantibodies (immunology) Child Child, Preschool Diabetes Mellitus, Type 1 (genetics, immunology) Genotype HLA-DQ Antigens (chemistry, genetics, immunology) HLA-DQ alpha-Chains Humans Infant Infant, Newborn Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Restriction Fragment Length Protein Conformation T-Lymphocytes (immunology)

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