Human endogenous retrovirus IDDMK(1,2)22 and mouse mammary tumor virus superantigens differ in their ability to stimulate murine T cell hybridomas.
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.
Azar
Georges A
GA
Laboratoire d'Immunologie Moleculaire, Departement de Microbiologie et Immunologie, Universite de Montreal, CP 6128, Succ. Centre-Ville, Montréal, Quebec, Canada H3C 3J7.
Thibodeau
Jacques
J
D000818:Animals; D000956:Antigens, Viral; D001402:B-Lymphocytes; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D018089:Superantigens / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000956:Antigens, Viral; C107453:ERVK-18 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C095378:Mtv-7 superantigen, Mouse mammary tumor virus; D018089:Superantigens