Susceptibility to rheumatoid arthritis--the conformational equivalence hypothesis

The occurrence of the inappropriate immune response of rheumatoid arthritis is likely controlled by several alleles of class II DR beta chain genes of the major histocompatibility complex (MHC). These include certain of those that encode the serologically distinct DR1 and DR4 specificities. In a manner analogous to a segregation analysis, advantage was taken of ethnic differences in susceptibility associated with different alleles and parallel differences in the organization of the class II haplotypes that specify either similar or divergent serologic specificities. This permitted mapping of this disease susceptibility into a single equivalent polymorphic alpha helical conformation shared by each DR beta allelic product. This suggests that rheumatoid arthritis originates from a unitary immune recognition event initiated by particular class II MHC molecules.