COMPARATIVE-ANALYSIS OF B7-1 AND B7-2 COSTIMULATORY LIGANDS - EXPRESSION AND FUNCTION

Antigen-specific T cell activation requires the engagement of the T ce ll receptor (TCR) with antigen as well as the engagement of appropriat e costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and C TLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cel ls. Recently, B7-2 a second costimulatory ligand for CTLA4, was descri bed, demonstrating the potential complexity of costimulatory interacti ons. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 c an be expressed by multiple cell types, including B cells, T cells, ma crophages, and dendritic cells, all of which are therefore candidate p opulations for delivering costimulatory signals mediated by these mole cules; (b) stimulating B cells with either LPS or anti-IgD-dextran ind uced expression of both B7-1 and B7-2, and peak expression of both cos timulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than express ion of B7-1 at all times assayed after stimulation; (c) blocking of B7 -2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (I L-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated b y a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be i ndependently regulated by the same stimulus, providing an additional c omplexity in the mechanisms available for regulating costimulation and hence immune response.