HUMAN B7-1 IS MORE EFFICIENT THAN B7-2 IN PROVIDING CO-STIMULATION FOR ALLOANTIGEN-SPECIFIC T-CELLS

Besides a signal via the T cell receptor/CD3 complex, an additional co stimulatory signal is required for optimal T cell activation. This sig nal can be delivered by interaction of either B7-1 or B7-2 expressed b y antigen-presenting cells with CD28 on the T cells. Comparison of the function of B7-1 and B7-2 in different experimental animal systems ge nerated conflicting data on the roles for the co-stimulatory molecules . We therefore investigated whether there are differences between B7-1 and B7-2-mediated co-stimulation in an alloantigen-specific primary T cell response induced by B7-transfected human cell lines of epithelia l origin. Both transfected keratinocyte cell lines efficiently induce T cell proliferation and the ratios of stimulator versus responder cel ls are similar. The kinetics of proliferation and interleukin (IL)-2, IL-4 and interferon-gamma production are also comparable between both transfectant lines. However, despite equal B7 expression levels, it is consistently found that the magnitude of the B7-1-induced T cell prol iferation was higher than that of B7-2. Comparison of precursor freque ncies of helper T lymphocytes responsive with either B7-1 or B7-2 reve aled that the frequency of B7-1 responsive T cells was higher than tha t of B7-2, and that the frequency of cells activated by a combination of B7-1 and B7-2 did not differ significantly from that of B7-1 alone. We therefore conclude that the B7-2-responsive T cells are part of th e B7-1-responsive population, and that B7-1 on keratinocytes is more e fficient in providing co-stimulation for alloantigen-specific T cells.