A Molecular Basis for MHC Class II—Associated Autoimmunity

TLDR

MHC class II molecules present antigenic peptides to T cells, and polymorphisms in their genes influence immune specificity and are linked to autoimmune disease risk. The study identifies class II polymorphic amino‑acid residues strongly associated with susceptibility to insulin‑dependent diabetes mellitus, rheumatoid arthritis, and pemphigus vulgaris. These residues implicate specific MHC class II isotypes in disease susceptibility and point to new prophylactic and therapeutic strategies.

Abstract

Class II major histocompatibility (MHC) molecules have an immunoregulatory role. These cell-surface glycoproteins present fragments of protein antigens (or peptides) to thymus-derived lymphocytes (T cells). Nucleotide sequence polymorphism in the genes that encode the class II MHC products determines the specificity of the immune response and is correlated with the development of autoimmune diseases. This study identifies certain class II polymorphic amino acid residues that are strongly associated with susceptibility to insulin-dependent diabetes mellitus, rheumatoid arthritis, and pemphigus vulgaris. These findings implicate particular class II MHC isotypes in susceptibility to each disease and suggest new prophylactic and therapeutic strategies.