IMMUNOGLOBULIN FOLD CHARACTERISTICS OF B7-1(CD80) AND B7-2(CD86)

B7-1 and B7-2 are expressed on antigen-presenting cells and bind to th e CD28 and CTLA-4 receptors on T cells. These interactions trigger a c ostimulatory pathway that is essential for T-cell activation. B7-1 and B7-2 are members of the immunoglobulin superfamily (IgSF) and, despit e sharing common function, have only limited sequence similarity. The B7-1 extracellular region was previously subdivided into 2 IgSF domain s, an N-terminal V(ariable)-like domain, followed by a C(onstant)like domain. We recently reported that the V-like domains of B7-1 and B7-2 share some significant sequence similarities with 3 major histocompati bility complex (MHC)-encoded members of the IgSF. We have now applied inverse folding methodology to assess the compatibility of the B7-1 an d B7-2 extracellular region sequences with currently available 3-dimen sional structures. In these calculations, the sequences of the N-termi nal (V-like) domains in B7-1 and B7-2 were not compatible with known s tructures, including the IgSF V-set. In contrast, the sequences of the C-like domains were compatible with IgSF C-set structures and were be st recognized by the beta 2-microglobulin (beta 2m) domain of MHC Clas s I. A sequence comparison of the C-like domains in the B7 molecules s howed that 11 of 17 rigorously conserved residues in B7-1 and B7-2 are not IgSF C-1 set consensus residues. When mapped onto the correspondi ng positions of the beta 2m structure, the conserved residues in B7 cl uster on the surface, where they may interact with the B7 V-like domai n or other molecules.