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 only ∼25% sequence identity and is expressed earlier during an immune response. Here we show that human CD86 maintains similar (within ∼2- to 3-fold) overall receptor binding and T cell costimulatory properties as CD80. However, CD80 and CD86 did not bind equivalently to CTLA-4: CD80 bound Y100A, a form of CTLA4Ig with a mutation in the CDR3-like region, >200-fold better than did CD86; inhibition of CD80-mediated cellular responses required ∼100-fold lower CTLA4Ig concentrations; and CD80-CTLA4Ig complexes dissociated 5- to 8-fold more slowly. Thus, CD80 and CD86 utilize different binding determinants and have different kinetics of binding to CD28 and CTLA-4.