Cutting edge: dependence of TCR antagonism on Src homology 2 domain-containing protein tyrosine phosphatase activity

J Immunol. 2003 May 15;170(10):4891-5. doi: 10.4049/jimmunol.170.10.4891.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Catalytic Domain / genetics
  • Catalytic Domain / immunology
  • Cells, Cultured
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Enzyme Activation / genetics
  • Enzyme Activation / immunology
  • Gene Deletion
  • Genetic Vectors
  • Humans
  • Immunophenotyping
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein Tyrosine Phosphatases / physiology
  • Receptors, Antigen, T-Cell / antagonists & inhibitors*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • src Homology Domains / immunology*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, T-Cell
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn6 protein, mouse