Protein Science, Vol 3, Issue 11 2148-2150, Copyright © 1994 by Cold Spring Harbor Laboratory Press

FOR THE RECORD

Immunoglobulin fold characteristics of B7-1 (CD80) and B7-2 (CD86)

J. BAJORATH, R. J. PEACH and P. S. LINSLEY
Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Avenue, Seattle, Washington 98121

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 extra-cellular 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 MOLECULES65.
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