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 requi res costimulatory signals that have been shown to be mainly initiated through CD28. We analyzed the expression and function of the two ligan ds for CD28, B7-1 (CD80) and B7-2 (CD86), on human Langerhans cells (L C), the antigen-presenting cells from epidermis. Human LC freshly isol ated from epidermis (fLC) expressed significant level of B7-2. which w as increased upon a short culture in vitro. In contrast, B7-1 was unde tectable 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 monoclona l 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 CTLA4Ig binding on 3- day cultured LC, showing the absence of a third CTLA4 ligand. The fun ction 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 CTLA4Ig. but not anti-B7-1 mAb. strongly inhibited allogeneic. as well as recall antigen-induced T cell proliferation supported by f LC 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.