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© Research
Publication :

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in - 07 Feb 2005

Gerke, C., S. Falkow, and Y-h. Chien

Link to Pubmed [PMID] – 15699071

J Exp Med. 2005 Feb 7;201(3):361-71

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.

http://jem.rupress.org/content/201/3/361.long