Azar Georges A, Thibodeau Jacques
Laboratoire d'Immunologie Moleculaire, Departement de Microbiologie et Immunologie, Universite de Montreal, CP 6128, Succ. Centre-Ville, Montréal, Quebec, Canada H3C 3J7.
Immunol Lett. 2002 Apr 1;81(1):87-91. doi: 10.1016/s0165-2478(01)00340-6.
Recently, a newly identified human HERV-K18 like endogenous retrovirus (IDDMK(1,2)22) has been associated to the etiology of type I diabetes (IDDM). Although the exact mechanism remains unclear, it was postulated that the 3' end ORF product of the env gene of IDDMK(1,2)22 would trigger a V beta 7-specific human T cell expansion leading to their infiltration in the pancreas of afflicted patients and to the autoimmune destruction of the insulin-producing beta cells. Since then, such superantigen (SAg)-like activity as well as the association between the IDDMK(1,2)22 virus and IDDM pathogenesis have been challenged. To further characterize functionally the putative IDDMK(1,2)22-encoded SAg, we have cloned from human DNA the identical 462bp ORF sequence originally described. The IDDMK(1,2)22 ORF fragment was transfected in the same human B cell line (Raji) originally used as APC to demonstrate the V beta 7 specificity. The immunostimulatory potential of IDDM ORF was tested on murine T cell hybridomas and compared to the well-characterized mouse mammary tumor virus Mtv7 SAg transfected in the same conditions. A panel of 16 T cell hybridomas encompassing 14 different V betas was analyzed. We have failed to detect IDDMK(1,2)22-induced IL-2 production from any of these hybridomas, even those bearing the murine V beta 1 mV beta 1, V beta 4 or V beta 10 TcR beta chains which are most closely related to the human V beta 7 (hV beta 7). Our results suggest that IDDMK(1,2)22 ORF is devoid of superantigenic activity as defined by classical criteria.
最近，一种新发现的类似人类内源性逆转录病毒HERV-K18（IDDMK(1,2)22）与I型糖尿病（IDDM）的病因有关。尽管确切机制尚不清楚，但据推测，IDDMK(1,2)22的env基因3'端开放阅读框产物会引发Vβ7特异性人类T细胞扩增，导致它们浸润到患病患者的胰腺中，并导致产生胰岛素的β细胞发生自身免疫性破坏。从那时起，这种类似超抗原（SAg）的活性以及IDDMK(1,2)22病毒与IDDM发病机制之间的关联受到了质疑。为了进一步从功能上表征假定的IDDMK(1,2)22编码的SAg，我们从人类DNA中克隆了最初描述的相同的462bp开放阅读框序列。将IDDMK(1,2)22开放阅读框片段转染到最初用作抗原呈递细胞（APC）的同一人类B细胞系（Raji）中，以证明Vβ7特异性。在小鼠T细胞杂交瘤上测试IDDM开放阅读框的免疫刺激潜力，并与在相同条件下转染的特征明确的小鼠乳腺肿瘤病毒Mtv7 SAg进行比较。分析了一组包含14种不同Vβ的16个T细胞杂交瘤。我们未能从这些杂交瘤中的任何一个检测到IDDMK(1,2)22诱导的白细胞介素-2产生，即使是那些带有与人类Vβ7（hVβ7）最密切相关的小鼠Vβ1、mVβ1、Vβ4或Vβ10 TcRβ链的杂交瘤。我们的结果表明，按照经典标准定义，IDDMK(1,2)22开放阅读框缺乏超抗原活性。
