CD22 is a functional ligand for SH2 domain-containing protein-tyrosine phosphatase-1 in primary T cells

J Biol Chem. 2004 Nov 12;279(46):47783-91. doi: 10.1074/jbc.M402354200. Epub 2004 Sep 10.


The intracellular Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase (SHP-1) has been characterized as a negative regulator of T cell function, contributing to the definition of T cell receptor signaling thresholds in developing and peripheral mouse T lymphocytes. The activation of SHP-1 is achieved through the engagement of its tandem SH2 domains by tyrosine-phosphorylated proteins; however, the identity of the activating ligand(s) for SHP-1, within mouse primary T cells, is presently unresolved. The identification of SHP-1 ligand(s) in primary T cells would provide crucial insight into the molecular mechanisms by which SHP-1 contributes to in vivo thresholds for T cell activation. Here we present a combination of biochemical and yeast genetic analyses indicating CD22 to be a T cell ligand for the SHP-1 SH2 domains. Based on these observations we have confirmed that CD22 is indeed expressed on mouse primary T cells and capable of associating with SHP-1. Significantly, CD22-deficient T cells demonstrate enhanced proliferation in response to anti-CD3 or allogeneic stimulation. Furthermore, the co-engagement of CD3 and CD22 results in a raising of TCR signaling thresholds hence demonstrating a previously unsuspected functional role for CD22 in primary T cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • CD3 Complex / immunology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Intracellular Signaling Peptides and Proteins
  • Lectins / genetics
  • Lectins / immunology*
  • Ligands
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Molecular Sequence Data
  • Protein Phosphatase 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / immunology*
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sialic Acid Binding Ig-like Lectin 2
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Two-Hybrid System Techniques
  • ZAP-70 Protein-Tyrosine Kinase
  • src Homology Domains*


  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD3 Complex
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • Intracellular Signaling Peptides and Proteins
  • Lectins
  • Ligands
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Sialic Acid Binding Ig-like Lectin 2
  • Protein-Tyrosine Kinases
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse
  • Protein Phosphatase 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn6 protein, mouse