Murine Vbeta3+ and Vbeta7+ T Cell Subsets Are Specific Targets for the HERV-K18 Env Superantigen

Superantigens are a class of proteins that are derived from microorganisms and have the unique characteristic of stimulating T cells in a TCR Vbeta-specific manner, causing massive T cell proliferation and immune deregulation. For this reason, superantigens have been implicated in the development of...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2006-09, Vol.177 (5), p.3178-3184
Main Authors: Tai, Albert K, Lin, Miao, Chang, Francesca, Chen, Gang, Hsiao, Francis, Sutkowski, Natalie, Huber, Brigitte T
Format: Article
Language:English
Subjects:
Animals
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Cell Line
Humans
Interleukin-2 - biosynthesis
Membrane Proteins - genetics
Membrane Proteins - immunology
Membrane Proteins - metabolism
Mice
Mice, Transgenic
Receptors, Antigen, T-Cell, alpha-beta - immunology
Superantigens - genetics
Superantigens - immunology
Superantigens - metabolism
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Superantigens are a class of proteins that are derived from microorganisms and have the unique characteristic of stimulating T cells in a TCR Vbeta-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-alpha treatment and EBV infection and stimulates human Vbeta13+ 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 Vbeta3+ and Vbeta7+ T cells in mice. The definition of the murine Vbeta 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.
ISSN:0022-1767
1550-6606