CD80 (B7-1) BINDS BOTH CD28 AND CTLA-4 WITH A LOW-AFFINITY AND VERY FAST KINETICS

The structurally related T cell surface molecules CD28 and CTLA-4 inte ract with cell surface ligands CD80 (B7-1) and CD86 (B7-2) on antigen- presenting cells (APC) and modulate T cell antigen recognition. Prelim inary reports have suggested that CD80 binds CTLA-4 and CD28 with affi nities (K-d values similar to 12 and similar to 200 nM, respectively) that are high when compared with other molecular interactions that con tribute to T cell-APC recognition. In the present study, we use surfac e plasmon resonance to measure the affinity and kinetics of CD80 bindi ng to CD28 and CTLA-4. At 37 degrees C, soluble recombinant CD80 bound to CTLA-4 and CD28 with K-d values of 0.42 and 4 mu M, respectively. Kinetic analysis indicated that these low affinities were the result o f very fast dissociation rate constants (k(off)); sCD80 dissociated fr om CD28 and CTLA-4 with k(off) values of greater than or equal to 1.6 and greater than or equal to 0.43 s(-1), respectively. Such rapid bind ing kinetics have also been reported for the T cell adhesion molecule CD2 and may be necessary to accommodate dynamic T cell-APC contacts an d to facilitate scanning of APC for antigen.