LINKAGE OF FAULTY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I TO AUTOIMMUNE DIABETES
LINKAGE OF FAULTY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I TO AUTOIMMUNE DIABETES
复制标题
DOI：
10.1126/science.1763324
复制
发表时间：
1991-12-20
期刊：
影响因子：
56.9
通讯作者：
GUO, J
中科院分区：
文献类型：
--
作者：
FAUSTMAN, D;LI, XP;GUO, J
胰岛细胞是 I 型糖尿病自身免疫反应的目标。在自身免疫性糖尿病的非肥胖糖尿病（NOD）小鼠模型中，主要组织相容性复合物（MHC）I类蛋白的表达与糖尿病呈负相关。在这只小鼠中，推定的 MHC I 类肽转运蛋白的 MHC II 类相关基因也存在突变。由于不产生 β-2-微球蛋白而缺乏 MHC I 类表达的小鼠也会患上迟发性自身免疫性糖尿病。在 I 型糖尿病患者的细胞中，I 类 MHC 的表达降低；被归类为最有可能出现高血糖的糖尿病前期患者亚群的 MHC I 类也较低。糖尿病患者的 T 细胞对自身抗原的反应存在缺陷。在患有糖尿病的基因相同的双胞胎中，缺陷似乎存在于抗原呈递细胞中。因此，表面 MHC I 类蛋白的缺乏与自身免疫性糖尿病有关。随之而来的抗原呈递缺陷可能会损害自我耐受的发展，从而导致自身免疫性疾病。
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.