HUMAN B7-1 (CD80) AND B7-2 (CD86) BIND WITH SIMILAR AVIDITIES BUT DISTINCT KINETICS TO CD28 AND CTLA-4 RECEPTORS

B7-0 or B7-2 (CD86) is a T cell costimulatory molecule that binds the same receptors (CD28 and CTLA-4) as B7-1 (CD80), but shares with it on ly similar to 25% sequence identity and is expressed earlier during an immune response. Here we show that human CD86 maintains similar (with in similar to 2- to 3-fold) overall receptor binding and T cell costim ulatory properties as CD80. However, CD80 and CD86 did not bind equiva lently to CTLA-4: CD80 bound Y100A, a form of CTLA4lg with a mutation in the CDR3-like region, >200-fold better than did CD86; inhibition of CD80-mediated cellular responses required similar to 100-fold lower C TLA4lg concentrations; and CD80-CTLA4lg complexes dissociated 5- to 8- fold more slowly. Thus, CD80 and CD86 utilize different binding determ inants and have different kinetics of binding to CD28 and CTLA-4.