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

Neely E Kilgore1, Jenny D Carter, Ulrike Lorenz

  • 1Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 8, 2003
PubMed

Insights

Antagonist peptides inhibit T cell responses through a newly identified mechanism involving Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1). Increased SHP-1 activity is crucial for this T cell antagonism.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The precise mechanism by which antagonist peptides inhibit T cell responses remains unclear.
  • Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1) is known to be vital for the negative regulation of lymphocyte signaling.

Purpose of the Study:

  • To investigate the potential role of SHP-1 in the process of T cell antagonism.
  • To elucidate the molecular underpinnings of T cell response inhibition by antagonist peptides.

Main Methods:

  • Utilized mice deficient in SHP-1 to assess its function in T cell signaling.
  • Measured SHP-1 activity in CD4(+) T cells during antagonism.
  • Assessed the effect of removing functional SHP-1 on T cell antagonism.

Main Results:

  • Demonstrated a significant increase in SHP-1 activity during the antagonism of CD4(+) T cells.
  • Showed that the absence of functional SHP-1 abrogates the antagonistic effect on these T cells.

Conclusions:

  • T cell antagonism is mediated by a negative intracellular signal.
  • This negative signaling pathway is dependent on the activity of SHP-1.

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