CD82, member of the tetra-span-transmembrane protein family, is a costimulatory protein for T cell activation

Abstract

It is now well documented that full activation of T cells requires a two-signal triggering that can be mimicked, in the absence of accessory cells, by co-immobilization of mAbs directed to stimulatory/accessory molecules (CD2, CD3, CD28, adhesion molecules, etc.). In this report, we describe that engagement of CD82 can delivery such a costimulatory signal for full activation of the human T cell line Jurkat, leading to strong IL-2 production and cell differentiation. The CD82 Ag, which belongs to the new tetra-span-transmembrane family (CD9, CD37, CD53, CD63, and CD81 (TAPA-1)), has been identified originally in our laboratory for its enhanced expression on three LAK-susceptible cell lines, and has been characterized as an activation/differentiation marker of mononuclear cells. Jurkat cells, stimulated in vitro by co-immobilization of anti-CD82 and anti-CD3 mAbs, produced high levels of IL-2, became strongly adherent to plastic dishes, and developed dendritic processes. These morphologic changes, associated with a total arrest of cell proliferation, were not the result of cell death but rather of cell differentiation, as shown by an increase in their metabolic activity. Costimulation through both CD82 and CD3 induced up-regulation of both IL-2 and IFN-gamma mRNA synthesis (but not of IL-4) and an increased expression of HLA class I molecules at the cell surface, which was inhibited by anti-IFN-gamma Ab.