Linkage of faulty major histocompatibility complex class I to autoimmune diabetes.
Pancreatic islet cells are the targets of an autoimmune response in type I diabetes. In the nonobese diabetic (NOD) mouse model of autoimmune diabetes, expression of major histocompatibility complex (MHC) class I proteins was inversely correlated with diabetes; in this mouse a mutation in the MHC class II-linked gene for the putative MHC class I peptide transporter was also present. Mice deficient in MHC class I expression because they do not produce beta 2-microglobulin also developed late onset autoimmune diabetes. In cells from humans with type I diabetes expression of MHC class I was decreased; subsets of prediabetics categorized as most likely to become hyperglycemic also had low MHC class I. T cell responses to self antigens are faulty in diabetics. In sets of genetically identical twins that are discordant for diabetes, the defect appeared to reside with the antigen presenting cell. Thus, a lack of surface MHC class I protein is associated with autoimmune diabetes; the concomitant defect in antigen presentation may impair the development of self tolerance, which could result in autoimmune disease.
Faustman
D
D
Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Charlestown 02129.
Li
X P
XP
Lin
H Y
HY
Fu
Y E
YE
Eisenbarth
G
G
Avruch
J
J
Guo
J
J
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D004200:Diseases in Twins; D005434:Flow Cytometry; D015870:Gene Expression; D005805:Genes, MHC Class I; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology