Functional analysis of CD82 in the early phase of T cell activation: roles in cell adhesion and signal transduction

To define T cell co‐stimulatory molecules that work in the early phase of T cell activation, we established monoclonal antibodies (mAb) that inhibit or enhance T cell activation by the histiocytic leukemia cell line U937. One of the mAb, 53H5, which recognized both T cells and U937, was identified to bind to CD82 by expression cloning. Functional analyses of CD82 revealed that 1) CD82 needs to exist on both T cells and U937 for the full activation of T cells; 2) CD82 expression is up‐regulated on both T cells and U937 by stimulation such as CD3 ligation or treatment with phorbol 12‐myristate 13‐acetate; 3) overexpression of CD82 enhances both homotypic and heterotypic cell adhesion betweenT cells and U937; 4) CD82 signal co‐stimulates T cells and the signal works synergistically with the CD28‐mediated T cell co‐stimulation signal; 5) in mixed leukocyte reactions using U937 as stimulator cells, CD82 overexpression on U937 correlates with the higher allogeneicity of U937 cells. These results indicate that CD82 co‐stimulates T cells not only by sending intra‐T cell signals that work synergistically with CD28 signals but also by inducing enhanced T cell‐antigen‐presenting cell interaction.