title: Enhancement of T-cell activation by the CD43 molecule whose expression is defective in Wiskott-Aldrich syndrome.
abstract: CD43 (sialophorin, leukosialin, leukocyte large sialoglycoprotein), a heavily sialylated molecule found on most leukocytes and platelets, was initially identified as a major glycoprotein of mouse, rat and human T cells. CD43 expression is defective on the T cells of males with the Wiskott-Aldrich syndrome, an X chromosome-linked recessive immunodeficiency disorder. Affected males are susceptible to opportunistic infections and do not respond to polysaccharide antigens, reflecting defects in cytotoxic and helper T-cell functions. Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes, and one such antibody has been shown to activate T cells directly. To investigate a possible physiological role for CD43, a complementary DNA encoding the human protein was introduced into an antigen-responsive murine T-cell hybridoma. We observed that CD43 enhances the antigen-specific activation of T cells and that the intracellular domain of CD43, which is hyperphosphorylated during T-cell activation, is required for this function. We also found that antigen-presenting cells can bind specifically to immobilized purified CD43 and that the binding can be inhibited by liposomes containing CD43 as well as by anti-CD43 monoclonal antibodies.
authors.affiliation: Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.forename: Y J
authors.initials: YJ
authors.lastname: Rosenstein
authors.forename: E
authors.initials: E
authors.lastname: Remold-O'Donnell
authors.forename: B E
authors.initials: BE
authors.lastname: Bierer
authors.forename: F S
authors.initials: FS
authors.lastname: Rosen
authors.forename: S J
authors.initials: SJ
authors.lastname: Burakoff
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D003001:Cloning, Molecular; D006801:Humans; D051917:Leukosialin; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D010957:Plasmids; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins; C497863:Spn protein, mouse