STRUCTURAL DIFFERENCES BETWEEN HLA-DQ MOLECULES ASSOCIATED WITH MYASTHENIA-GRAVIS CHARACTERIZED BY MOLECULAR MODELING

Myasthenia gravis (MG) is characterized by muscle weakness due to auto immunity against the nicotinic acetylcholine receptor (nAChR). MG is a ssociated with polymorphisms in HLA-DQ genes and the aim of the presen t study was to characterize structural differences in the peptide bind ing groove of HLA-DQ molecules positively and negatively associated wi th MG. Three dimensional models of the positively associated DQ2 (DQB1 02) and negatively associated DQ6 (DQB1*O603) molecules were construc ted by homology modeling techniques. The differences in peptide bindin g properties were primarily localized to peptide-anchor pockets P7 and P9, which might be of importance for the binding of disease-associate d peptides from the nAChR. (C) 1998 Elsevier Science B.V. All rights r eserved.