Natalie Sutkowski
Tufts University
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Publication
Featured researches published by Natalie Sutkowski.
Immunity | 2001
Yves Stauffer; Samuel Marguerat; Françoise Meylan; Catherine Ucla; Natalie Sutkowski; Brigitte T. Huber; Thierry Pelet; Bernard Conrad
Abstract 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-α (IFN-α) are tightly associated with the onset of autoimmunity. Here we establish a link between viral infections and IFN-α-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-α and this is sufficient to stimulate Vβ7 T cells to levels comparable to transfectants constitutively expressing HERV-K18 SAgs. Endogenous SAgs induced via IFN-α by viral infections is a novel mechanism through which environmental factors may cause disease in genetically susceptible individuals.
Journal of Virology | 2004
Natalie Sutkowski; Gang Chen; German Calderon; Brigitte T. Huber
ABSTRACT Superantigens are microbial proteins that strongly stimulate T cells. We described previously that the Epstein-Barr virus (EBV) transactivates a superantigen encoded by the human endogenous retrovirus, HERV-K18. We now report that the transactivation is dependent upon the EBV latent cycle proteins. Moreover, LMP-2A is sufficient for induction of HERV-K18 superantigen activity.
Virology | 2009
Francis C. Hsiao; Albert K. Tai; Agnes Deglon; Natalie Sutkowski; Richard Longnecker; Brigitte T. Huber
EBV encodes latent membrane protein (LMP)-2A that functions as a homologue of the activated BCR. We have previously shown that LMP-2A transactivates a human endogenous retrovirus, HERV-K18, in infected B-lymphocytes. The Env protein of HERV-K18 encodes a superantigen that strongly stimulates a large number of T cells. To delineate the mechanism through which LMP-2A transactivates HERV-K18 env, we tested a panel of tyrosine mutants of LMP-2A in a murine B lymphoma that stably harbors HERV-K18. Our analysis revealed that the immunoreceptor tyrosine-based activation motif (ITAM) of LMP-2A is important for HERV-K18 env transactivation. ITAM contains 2 tyrosines that initiate signaling cascades when both residues are phosphorylated. However, in our study, single-tyrosine mutants of ITAM still retained full induction of HERV-K18 env. After truncating 25 kb of genomic sequence downstream of HERV-K18, LMP-2A failed to transactivate HERV-K18 env. Thus, an LMP-2A-inducible element is located downstream of HERV-K18.
Journal of Immunology | 2006
Albert K. Tai; Miao Lin; Francesca Chang; Gang Chen; Francis C. Hsiao; Natalie Sutkowski; Brigitte T. Huber
Superantigens are a class of proteins that are derived from microorganisms and have the unique characteristic of stimulating T cells in a TCR Vβ-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-α treatment and EBV infection and stimulates human Vβ13+ 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 Vβ3+ and Vβ7+ T cells in mice. The definition of the murine Vβ 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.
Journal of Immunology | 2001
Ping-Ning Hsu; Paula Wolf Bryant; Natalie Sutkowski; Brian McLellan; Hidde L. Ploegh; Brigitte T. Huber
Mouse mammary tumor viruses encode superantigens that interact with MHC class II proteins and stimulate T cells. We show here that presentation of mouse mammary tumor virus superantigen does not require DM. Furthermore, we have identified a strong class II peptide binding motif in the Mtv-7 superantigen, and we show that this motif is necessary for association with class II molecules in in vitro translation and in vivo functional assays. Our results suggest that endogenously synthesized viral superantigen can bind to MHC class II heterodimers during biosynthesis in the endoplasmic reticulum in a manner analogous to that used by the class II-associated invariant chain.
Immunity | 2001
Natalie Sutkowski; Bernard Conrad; David A. Thorley-Lawson; Brigitte T. Huber
Journal of Experimental Medicine | 1996
Natalie Sutkowski; T Palkama; Cristina Ciurli; Rafick-Pierre Sekaly; David A. Thorley-Lawson; Brigitte T. Huber
The Journal of Rheumatology | 2005
Jocelyn Sicat; Natalie Sutkowski; Brigitte T. Huber
Microbiological Research | 1996
Brigitte T. Huber; Ping-Ning Hsu; Natalie Sutkowski
Archive | 2001
Brigitte T. Huber; David A. Thorley-Lawson; Natalie Sutkowski