Abstract
B7-1 and B7-2 are generally thought to have comparable structures and affinities for their receptors, CD28 and CTLA-4, each of which is assumed to be bivalent. We show instead (1) that B7-2 binds the two receptors more weakly than B7-1, (2) that, relative to its CTLA-4 binding affinity, B7-2 binds CD28 2- to 3-fold more effectively than B7-1, (3) that, unlike B7-1, B7-2 does not self-associate, and (4) that, in contrast to CTLA-4 homodimers, which are bivalent, CD28 homodimers are monovalent. Our results indicate that B7-1 markedly favors CTLA-4 over CD28 engagement, whereas B7-2 exhibits much less bias. We propose that the distinct structures and binding properties of B7-1 and B7-2 account for their overlapping but distinct effects on T cell responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Abatacept
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology*
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Antigens, Differentiation / chemistry
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Antigens, Differentiation / genetics
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Antigens, Differentiation / immunology*
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B7-1 Antigen / genetics
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B7-1 Antigen / immunology*
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B7-2 Antigen
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CD28 Antigens / chemistry
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CD28 Antigens / genetics
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CD28 Antigens / immunology*
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CHO Cells
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CTLA-4 Antigen
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Cricetinae
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Immunoconjugates*
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Kinetics
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Solutions
Substances
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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CTLA-4 Antigen
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Immunoconjugates
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Membrane Glycoproteins
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Recombinant Fusion Proteins
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Solutions
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Abatacept