MEM‐59 monoclonal antibody detects a CD43 epitope involved in lymphocyte activation

Abstract

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.