Expression and function of B7‐1 (CD80) and B7‐2 (CD86) on human epidermal Langerhans cells

In addition to T cell receptor triggering, activation of T cells requires co‐stimulatory signals that have been shown to be mainly initiated through CD28. We analyzed the expression and function of the two ligands for CD28, B7‐1 (CD80) and B7‐2 (CD86), on human Langerhans cells (LC), the antigen‐presenting cells from epidermis. Human LC freshly isolated from epidermis (fLC) expressed significant level of B7‐2, which was increased upon a short culture in vitro. In contrast, B7‐1 was undetectable on fLC but appeared at the cell surface after a 3‐day culture in vitro. Pre‐incubation of 18‐h cultured LC with anti‐B7‐2 monoclonal antibodies (mAb) was sufficient to abrogate the binding of CTLA4‐Ig fusion protein, while a combination of both mAb against B7‐1 and B7‐2 was necessary to obtain a complete inhibition of CTLA4‐Ig binding on 3‐day cultured LC, showing the absence of a third CTLA4 ligand. The function of B7‐1 and B7‐2 on human LC has been analyzed by adding mAb at the beginning of mixed epidermal cell lymphocyte reactions. Anti‐B7‐2 mAb and CTLA4‐Ig, but not anti‐B7‐1 mAb, strongly inhibited allogeneic, as well as recall antigen‐induced T cell proliferation supported by fLC or 3‐day cultured LC. Collectively, these results demonstrate that B7‐2 is the major ligand for CD28/CTLA4 at the LC surface and that it plays a crucial role in human LC co‐stimulatory function with little, if any, dependence on B7‐1 expression.