B7-1 and B7-2: similar costimulatory ligands with different biochemical, oligomeric and signaling properties.
B7-1 and B7-2 are homologous costimulatory ligands expressed on the surface of antigen presenting cells (APCs). Binding of these molecules to the T cell costimulatory receptors, CD28 and CTLA-4, is essential for the activation and regulation of T cell immunity. Despite strong structural similarities, B7-1 and B7-2 exhibit different biochemical features, and their binding to the costimulatory receptors results in distinct T cell functional outcomes. Using photobleaching based fluorescence resonance energy transfer (FRET), our previous studies have demonstrated that B7-1 and B7-2 have different cell surface oligomeric states. While B7-1 is present as a dimer, B7-2 exists as a monomer on the cell surface suggesting that the unique cell surface oligomeric states of the costimulatory ligands may play a key role in the regulation of T cell responses. Moreover, signaling via B7-1 and B7-2 in dendritic cells has been reported to be dependent on their simultaneous expression, raising the possibility that their direct interaction or their involvement in synergistic signaling pathways may play a role in the function of antigen presenting cells. We discuss physiological relevance of distinct oligomeric states of B7-1 and B7-2 and address whether these molecules can associate with one another on the cell surface to form hetero-oligomers. Our findings suggest that B7-1 and B7-2 do not form hetero-oligomers, underscoring the biological relevance of dimeric and monomeric state of B7-1 and B7-2, respectively.
Bhatia
Sumeena
S
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Edidin
Michael
M
Almo
Steven C
SC
Nathenson
Stanley G
SG
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D018122:B7-1 Antigen / Q000032:analysis / Q000378:metabolism*; D051940:B7-2 Antigen / Q000032:analysis / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; 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; C556706:CTLA4 protein, human; D008024:Ligands