A Molecular Basis for MHC Class II—Associated Autoimmunity

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.

Sequence of i‐e genes from autoimmune new zealand white mice

“…Close associations of class I1 MHC alleles with a variety of human a s well as animal autoimmune diseases have been documented (16). In several instances, disease susceptibility or resistance correlates with either a particular amino acid at a single position or within a short distance.…”

“…In several instances, disease susceptibility or resistance correlates with either a particular amino acid at a single position or within a short distance. For example, residues 70-74 in the third hypervariable region of DRPl exert dominant effects in disease susceptibility to rheumatoid arthritis (16,17). In diabetes mellitus, amino acid 57 of DQP appears to confer susceptibility to disease if it is alanine, serine, or valine, or resistance to disease if it is aspartic acid.…”

DNA typing of HLA in the patients with moyamoya disease

“…The HLA plays an important role in controlling the immune system and is known to be associated with various diseases such as auto-immune diseases (Todd et al, 1988;Sasazuki et al, 1983), infectious diseases (Hirayama et al, 1987;Nishimura and Sasazuki, 1987) and virus-associated tumors (Burt et al, 1994).…”

Immuno- and genetic therapy in autoimmune diseases

“…The imbalance of cytokines has been well characterized 135 and the high levels of pro-inflammatory cytokines counteract the presence of inhibitory cytokines such as TGF␤, IL-10 or cytokine inhibitors such as soluble TNF receptors (TNF-Rs). Susceptibility to RA has been mainly correlated with the MHC class II locus in particular with HLA-DR4 [136][137][138][139] which is associated with severity of disease and some association was found also with the class III locus. 140 Immunotherapies for RA have examined the effects of inhibiting the inflammatory TNF-driven cytokine cascade using anti-TNF antibody 141 or TNF-R-Ig fusion proteins.…”