Cutting edge: dependence of TCR antagonism on Src homology 2 domain-containing protein tyrosine phosphatase activity.
The mechanism by which antagonist peptides inhibit T cell responses is unknown. Mice deficient in Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1) have revealed its importance in the negative regulation of lymphocyte signaling. We investigated a possible role for SHP-1 in T cell antagonism and demonstrate, for the first time, a substantial increase in SHP-1 activity during antagonism of CD4(+) T cells. Furthermore, the removal of functional SHP-1 prevents antagonism in these cells. Our data demonstrate that T cell antagonism occurs via a negative intracellular signal that is mediated by SHP-1.
Kilgore
Neely E
NE
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Carter
Jenny D
JD
Lorenz
Ulrike
U
Evavold
Brian D
BD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D005822:Genetic Vectors; D006801:Humans; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018909:src Homology Domains / Q000276:immunology*
D047908:Intracellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse