MEM-59 monoclonal antibody detects a CD43 epitope involved in lymphocyte activation.
Previous studies on T cell activation via CD43 antigen stimulation were limited to the use of L10, a monoclonal antibody (mAb) recognizing a sialic acid-independent epitope on the CD43 molecule. Here we study the CD43 mAb MEM-59, which recognizes a neuraminidase-sensitive epitope on the CD43 molecule, for its ability to activate T lymphocytes. The antibody by itself is able to stimulate proliferation of peripheral blood mononuclear cells (PBMC) in a monocyte-dependent fashion, and to act synergistically with the mitogen phorbol 12-myristate 13-acetate. It is demonstrated that the monocyte dependence of MEM-59-induced proliferation of peripheral blood lymphocytes (PBL) cannot be attributed to cross-linking via Fc receptors on monocytes alone: F(ab')2 fragments of MEM-59 are at least as effective as intact IgG in the induction of PBMC proliferation. The effects of MEM-59 reported here are distinct in important ways from those reported for L10. Our proliferation data are extended by the observation that MEM-59 mAb induces mobilization of intracellular Ca2+ in PBMC and in the T cell line Jurkat, while the CD3/TcR-negative Jurkat derived-mutant J.TR3-T3.5 exhibits defective signaling compared to the parent cell line. Moreover, CD3 and CD43 are shown to be present jointly in a large complex in a mild detergent lysate of the T cell line HPB-ALL. These data indicate a physical and functional association between CD3/TcR and CD43 pathways, suggesting a role for CD43 as a co-stimulatory molecule in CD3/TcR signaling, especially in T cell-antigen-presenting cell interactions.
Alvarado
M
M
Department of Immunology, Medical School Hannover, Germany.
Klassen
C
C
Cerny
J
J
Horejsí
V
V
Schmidt
R E
RE
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD; D002455:Cell Division / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D012795:Sialoglycoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000939:Epitopes; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins