The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation.
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.
Gerke
Christiane
C
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Falkow
Stanley
S
Chien
Yueh-hsiu
YH
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism; D015009:Yersinia Infections / Q000276:immunology; D015011:Yersinia pseudotuberculosis / Q000276:immunology* / Q000472:pathogenicity*
D048868:Adaptor Proteins, Signal Transducing; D001425:Bacterial Outer Membrane Proteins; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D002118:Calcium