The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published 7 February 2005. doi:10.1084/jem.20041120
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 3, 361-371
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ARTICLE

 The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation

Christiane Gerke, Stanley Falkow, and Yueh-hsiu Chien

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

CORRESPONDENCE Yueh-hsiu Chien: chien{at}stanford.edu

T cell responses are critical to the survival of Yersinia-infected animals. Yersinia have the ability to directly suppress T lymphocyte activation through the virulence factor YopH, a tyrosine phosphatase. Using single cell video microscopy and FACS analysis, here we show that even an average of one Yersinia per T cell is sufficient to inhibit or alter T cell responses. This efficient inhibition is traced to specific targeting by YopH of the adaptor proteins, linker for activation of T cells (LAT) and SH2-domain–containing leukocyte protein of 76 kD (SLP-76), which are crucial for T cell antigen receptor (TCR) signaling. A catalytically inactive YopH translocated via the type III secretory pathway from the bacteria into T cells primarily binds to LAT and SLP-76. Furthermore, among the proteins of the TCR signaling pathway, the tyrosine phosphorylation levels of LAT and SLP-76 are the most affected in T cells exposed to low numbers of Yersinia pseudotuberculosis. This is the first example showing that a pathogen targets these adaptor proteins in the TCR signaling pathway, suggesting a novel mechanism by which pathogens may efficiently alter T cell–mediated immune responses.

Abbreviations used: FAK, focal adhesion kinase; Gads, Grb2-like adaptor protein downstream of Shc; GST, glutathion S-transferase; HA, hemagglutinin; HRP, horseradish peroxidase; LAT, linker for activation of T cells; MCC, moth cytochrome c; MOI, multiplicity of infection; PH, pleckstrin homology; PI3K, phosphoinositide 3–kinase; SLAP-130, SLP-76–associated phosphoprotein of 130 kD; SLP-76, SH2-domain–containing leukocyte protein of 76 kD; YFP, yellow fluorescent protein.


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