Conrad B, Weissmahr R N, Böni J, Arcari R, Schüpbach J, Mach B
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Cell. 1997 Jul 25;90(2):303-13. doi: 10.1016/s0092-8674(00)80338-4.
Microbial superantigens (SAGs) have been implicated in the pathogenesis of human autoimmune diseases. Preferential expansion of the Vveta7 T cell receptor positive T cell subset in patients suffering from acute-onset type I diabetes has indicated the presence of a surface membrane-bound SAG. Here, we have isolated a novel mouse mammary tumor virus-related human endogenous retrovirus. We further show that the N-terminal moiety of the envelope gene encodes an MHC class II-dependent SAG. We propose that expression of this SAG, induced in extrapancreatic and professional antigen-presenting cells, leads to beta-cell destruction via the systemic activation of autoreactive T cells. The SAG encoded by this novel retrovirus thus constitutes a candidate autoimmune gene in type I diabetes.
微生物超抗原（SAGs）与人类自身免疫性疾病的发病机制有关。急性发作的I型糖尿病患者中Vveta7 T细胞受体阳性T细胞亚群的优先扩增表明存在一种表面膜结合的SAG。在此，我们分离出一种新型的小鼠乳腺肿瘤病毒相关的人类内源性逆转录病毒。我们进一步表明，包膜基因的N末端部分编码一种MHC II类依赖性SAG。我们提出，在胰腺外和专职抗原呈递细胞中诱导产生的这种SAG的表达，通过自身反应性T细胞的全身激活导致β细胞破坏。因此，这种新型逆转录病毒编码的SAG构成了I型糖尿病中的一个候选自身免疫基因。
