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3+ and V
7+ T Cell Subsets Are Specific Targets for the HERV-K18 Env Superantigen1
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111
Superantigens are a class of proteins that are derived from microorganisms and have the unique characteristic of stimulating T cells in a TCR V
-specific manner, causing massive T cell proliferation and immune deregulation. For this reason, superantigens have been implicated in the development of multiple diseases. We have previously identified and cloned an EBV-associated superantigen, human endogenous retrovirus (HERV)-K18 envelope protein (Env). This superantigen is transactivated upon IFN-
treatment and EBV infection and stimulates human V
13+ T cells. Due to the limited scope of work that can be conducted with human samples and the complexity of HERVs in general, we set out to study the physiological effects of HERV-K18 Env in a murine model. In this report, we demonstrate the superantigen activity of HERV-K18 Env in mice and describe the generation of HERV-K18 transgenics, using a bacterial artificial chromosome as transgenes that allow the faithful reproduction of the expression pattern of this human provirus. From our in vitro and in vivo results we conclude that HERV-K18 Env stimulates V
3+ and V
7+ T cells in mice. The definition of the murine V
specificity and the establishment of a transgenic model will permit the investigation of the role of this superantigen in the life cycle of EBV and its implicated diseases.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant R01 AI14910, the GRASP (Gastroenterology Research on Absorptive and Secretory Processes) Center, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases P30 DK34928, and the Eshe Fund (to B.T.H.).
2 Current address: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425.
3 Address correspondence and reprint requests to Dr. Brigitte T. Huber, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111. E-mail address: Brigitte.huber{at}tufts.edu
4 Abbreviations used in this paper: HERV, human endogenous retrovirus; Env, envelope protein; BAC, bacterial artificial chromosome; env, envelope gene; LCL, lymphoblastoid cell line; MMTV, Murine mammary tumor virus.
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