The B7 family of immune-regulatory ligands

The B7 family consists of structurally related, cell- surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. Activation of T and B lymphocytes is initiated by engagement of cell- surface, antigen- specific T- cell receptors or B- cell receptors, but additional signals delivered simultaneously by B7 ligands determine the ultimate immune response. These ' costimulatory' or ' coinhibitory' signals are delivered by B7 ligands through the CD28 family of receptors on lymphocytes. Interaction of B7- family members with costimulatory receptors augments immune responses, and interaction with coinhibitory receptors attenuates immune responses. There are currently seven known members of the family: B7.1 ( CD80), B7.2 ( CD86), inducible costimulator ligand ( ICOS- L), programmed death- 1 ligand ( PD- L1), programmed death-2 ligand ( PD- L2), B7- H3, and B7- H4. Members of the family have been characterized predominantly in humans and mice, but some members are also found in birds. They share 20-40% amino- acid identity and are structurally related, with the extracellular domain containing tandem domains related to variable and constant immunoglobulin domains. B7 ligands are expressed in lymphoid and non- lymphoid tissues. The importance of the family in regulating immune responses is shown by the development of immunodeficiency and autoimmune diseases in mice with mutations in B7- family genes. Manipulation of the signals delivered by B7 ligands has shown potential in the treatment of autoimmunity, inflammatory diseases and cancer.