Interferon-α-induced endogenous superantigen:: A model linking environment and autoimmunity

被引:110
作者
Stauffer, Y
Marguerat, S
Meylan, F
Ucla, C
Sutkowski, N
Huber, B
Pelet, T
Conrad, B [1 ]
机构
[1] Univ Geneva, Sch Med, Dept Genet & Microbiol, CH-1211 Geneva 4, Switzerland
[2] Tufts Univ, Dept Pathol, Boston, MA 02111 USA
关键词
D O I
10.1016/S1074-7613(01)00212-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We earlier proposed that a human endogenous retroviral (HERV) superantigen (SAg) IDDMK(1,2)22 may cause type I diabetes by activating autoreactive T cells. Viral infections and induction of interferon-alpha (IFN-alpha) are tightly associated with the onset of autoimmunity. Here we establish a link between viral infections and IFN-alpha -regulated SAg expression of the polymorphic and defective HERV-K18 provirus. HERV-K18 has three alleles, IDDMK(1,2)22 and two full-length envelope genes, that all encode SAgs. Expression of HERV-K18 SAgs is inducible by IFN-alpha. and this is sufficient to stimulate V beta7 T cells to levels comparable to transfectants constitutively expressing HERV-K18 SAgs. Endogenous SAgs induced via IFN-alpha by viral infections is a novel mechanism through which environmental factors may cause disease in genetically susceptible individuals.
引用
收藏
页码:591 / 601
页数:11
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