DNA sequence analysis of major histocompatibility complex (MHC) class II genes from humans and rodents with type 1 (insulin-dependent) diabetes indicates that a portion of MHC-linked genetic susceptibility in humans is determined by the HLA-DQA1 and -DQB1 loci. In this article John Todd summarizes recent advances in these studies. The conformation of DQ molecules and their levels of expression may influence the efficiency of autoantigen presentation and the degree of pancreatic beta cells destruction during disease development. Certain DAQ1 and DQB1 alleles correlate with decreased susceptibility to disease. The penetrance of class II alleles that are correlated with positive susceptibility may be influenced by environmental factors such as bacterial and viral infections.
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