UNCOVERING OF FUNCTIONAL ALTERNATIVE CTLA-4 COUNTER-RECEPTOR IN B7-DEFICIENT MICE

B7 delivers a costimulatory signal through CD28, resulting in interleu kin-2 secretion and T cell proliferation. Blockade of this pathway res ults in T cell anergy. The in vivo role of B7 was evaluated with B7-de ficient mice. These mice had a 70 percent decrease in costimulation of the response to alloantigen. Despite lacking B7 expression, activated B cells from these mice bound CTLA-4 and GL1 monoclonal antibody, dem onstrating that alternative CTLA-4 ligand or ligands exist. These rece ptors are functionally important because the residual allogenic mixed lymphocyte responses were blocked by CTLA4Ig. Characterization of thes e CTLA-4 ligands should lead to strategies for manipulating the immune response.