Different cell surface oligomeric states of B7-1 and B7-2: Implications for signaling

Sumeena Bhatia, Michael Edidin, Steven C. Almo, Stanley G. Nathenson

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

The costimulatory ligands B7-1 and B7-2 are expressed on the surface of antigen-presenting cells and interact with the costimulatory receptors CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expressed on T cells. Although B7-1 and B7-2 are homologous ligands having common receptors, they exhibit distinct biochemical features and roles in immune regulation. Several biochemical and structural studies have indicated differences in the oligomeric state of B7-1 and B7-2. However, the organization of B7 ligands on the cell surface has not been examined. By using photobleaching-based FRET (pbFRET), we demonstrate that B7-1 and B7-2 adopt different oligomeric states on the cell surface. Our study shows that B7-2 exists as a monomer on the cell surface whereas B7-1 exists predominantly as dimers on the cell surface. A series of mutations in B7-1 result in the expression of a predominantly monomeric species on the cell surface and validate the dimer interface proposed by prior crystallographic analysis. The difference in the oligomeric states of B7-1 and B7-2 provides insight into the geometric organization of the costimulatory receptor-ligand complexes in the immunological synapse and suggests constraints on signal transduction mechanisms involved in T cell activation.

Original languageEnglish (US)
Pages (from-to)15569-15574
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number43
DOIs
StatePublished - Oct 25 2005

Keywords

  • Oligomerization
  • Photobleaching FRET
  • T cell costimulation

ASJC Scopus subject areas

  • General

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