Structure and dimerization of a soluble form of B7-1

B7-1 (CD80) and B7-2 (CD86) are glycoproteins expressed on antigen-presenti ng cells. The binding of these molecules to the T cell homodimers CD28 and CTLA-4 (CD152) generates costimulatory and inhibitory signals in T cells, r espectively. The crystal structure of the extracellular region of B7-1 (sB7 -1), solved to 3 Angstrom resolution, consists of a novel combination of tw o Ig-like domains, one characteristic of adhesion molecules and the other p reviously seen only in antigen receptors. In the crystal lattice, sB7-1 une xpectedly forms parallel, 2-fold rotationally symmetric homodimers. Analyti cal ultracentrifugation reveals that sB7-1 also dimerizes in solution. The structural data suggest a mechanism whereby the avidity-enhanced binding of B7-1 and CTLA-4 homodimers, along with the relatively high affinity of the se interactions, favors the formation of very stable inhibitory signaling c omplexes.