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 the CD28 and CTLA-4 receptors on T cells. These interactions trigger a costimulatory pathway that is essential for T-cell activation. B7-1 and B7-2 are members of the immunoglobulin superfamily (IgSF) and, despite sharing common function, have only limited sequence similarity. The B7-1 extracellular region was previously subdivided into 2 IgSF domains, 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 histocompatibility complex (MHC)-encoded members of the IgSF. We have now applied inverse folding methodology to assess the compatibility of the B7-1 and B7-2 extracellular region sequences with currently available 3-dimensional structures. In these calculations, the sequences of the N-terminal (V-like) domains in B7-1 and B7-2 were not compatible with known structures, including the IgSF V-set. In contrast, the sequences of the C-like domains were compatible with IgSF C-set structures and were best recognized by the beta 2-microglobulin (beta 2m) domain of MHC Class I. A sequence comparison of the C-like domains in the B7 molecules showed 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 corresponding positions of the beta 2m structure, the conserved residues in B7 cluster on the surface, where they may interact with the B7 V-like domain or other molecules.
Bajorath
J
J
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Peach
R J
RJ
Linsley
P S
PS
D000595:Amino Acid Sequence; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000737:chemistry*; D051940:B7-2 Antigen; D017124:Conserved Sequence; D007136:Immunoglobulins / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D001613:beta 2-Microglobulin / Q000737:chemistry
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D001613:beta 2-Microglobulin