The interaction properties of costimulatory molecules revisited

Immunity. 2002 Aug;17(2):201-10. doi: 10.1016/s1074-7613(02)00362-x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, Differentiation / chemistry
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology*
  • B7-2 Antigen
  • CD28 Antigens / chemistry
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology*
  • CHO Cells
  • CTLA-4 Antigen
  • Cricetinae
  • Immunoconjugates*
  • Kinetics
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Solutions

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Immunoconjugates
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Solutions
  • Abatacept