Different cell surface oligomeric states of B7-1 and B7-2: implications for signaling.
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.
Bhatia
Sumeena
S
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Edidin
Michael
M
Almo
Steven C
SC
Nathenson
Stanley G
SG
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000737:chemistry; D018122:B7-1 Antigen / Q000737:chemistry*; D051940:B7-2 Antigen / Q000737:chemistry*; D018106:CD28 Antigens / Q000737:chemistry; D016466:CHO Cells; D060908:CTLA-4 Antigen; D006224:Cricetinae; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D008213:Lymphocyte Activation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen