The interaction properties of costimulatory molecules revisited.
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.
Nuffield Department of Clinical Medicine, The University of Oxford, John Radcliffe Hospital, Headington, United Kingdom.
Alison V
AV
Collins
Douglas W
DW
Brodie
Robert J C
RJ
Gilbert
Andrea
A
Iaboni
Raquel
R
Manso-Sancho
Björn
B
Walse
David I
DI
Stuart
P Anton
PA
van der Merwe
Simon J
SJ
Davis
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000943:Antigens, Differentiation / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016466:CHO Cells; D060908:CTLA-4 Antigen; D006224:Cricetinae; D018796:Immunoconjugates; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012996:Solutions
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D012996:Solutions; D000069594:Abatacept