HLA and susceptibility to type I diabetes. Hypothesis.

Positive associations between the antigens D(R)3 and D(R)4 and negative associations of D(R)2 have been reported with insulin dependent or type I diabetes mellitus. It has been suggested that susceptibility factor(s) associated with the D(R)3 and D(R)4 haplotypes and a resistance factor associated with the D(R)2 haplotype may be involved in the pathogenesis of the disease. We propose a hypothesis herein which attempts to unify these findings based on our present understanding suggesting (a) the existence of multiple antigenic determinants associated with any one D(R) haplotype and (b) the sharing of "single" D region encoded determinants between what we now refer to as different D(R) haplotypes. The hypothesis, in its simplest form, focuses on a single D region determinant which can be found associated at different frequencies with the various D haplotypes as potentially explaining the findings.