title: CD22 is a functional ligand for SH2 domain-containing protein-tyrosine phosphatase-1 in primary T cells.
abstract: 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.
authors.affiliation: Section of Infection and Immunity, Henry Wellcome Building for Biomedical Research in Wales, Cardiff University, Cardiff CF14 4XX, Wales, United Kingdom.
authors.forename: Jean G
authors.initials: JG
authors.lastname: Sathish
authors.forename: Jenna
authors.initials: J
authors.lastname: Walters
authors.forename: Jin Cai
authors.initials: JC
authors.lastname: Luo
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Johnson
authors.forename: Frances G
authors.initials: FG
authors.lastname: Leroy
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Kwang P
authors.initials: KP
authors.lastname: Kim
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.forename: R James
authors.initials: RJ
authors.lastname: Matthews
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D020798:Two-Hybrid System Techniques; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D017252:CD3 Complex; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse