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 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, resulting also in the modulation of interleukin production. Interaction of B7-family members with costimulatory receptors augments immune responses and interaction with coinhibitory receptors attenuates immune responses.
There are currently nine known members of the B7 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, B7-H4, VISTA (B7-H5) and B7-H7, and four known members of the CD28 family: CD28, CTLA-4 (CD152), ICOS, PD-1. The importance of the B7-CD28 superfamily in regulating immune responses is shown by the role of some members in the development of immunodeficiency and autoimmune diseases. Manipulation of the signals delivered by B7 ligands has shown potential in the treatment of autoimmunity, inflammatory diseases and cancer.
Other Immune Checkpoint Proteins
Immune Checkpoints Overview
TIMs – Regulating Immune Responses
The TIM (T cell/transmembrane, immunoglobulin and mucin) family plays a critical role in regulating immune responses, including allergy, asthma, transplant tolerance, autoimmunity and the response to viral infections. The unique structure of TIM immunoglobulin variable region domains allows highly specific recognition of phosphatidylserine (PtdSer), exposed on the surface of apoptotic cells. Tim-1, important for asthma and allergy, is preferentially expressed on T-helper 2 (Th2) cells and functions as a potent costimulatory molecule for T cell activation. Tim-1 also mediates phagocytosis of apoptotic cells. Tim-2 is preferentially up-regulated during Th2 differentiation and functions as a potent costimulatory molecule for T cell immunity. Tim-3 is preferentially expressed on Th1, Tc1 (cytotoxic T cell Type 1) and Th17 cells and generates an inhibitory signal resulting in apoptosis of Th1 and Tc1 cells. Tim-3 is also expressed on some dendritic cells and can mediate phagocytosis of apoptotic cells and cross-presentation of antigens. Tim-4 is exclusively expressed on antigen-presenting cells, where it mediates phagocytosis of apoptotic cells and plays an important role in maintaining tolerance.
Under physiological conditions, interaction of Tim-3 with its ligand galectin-9 silences Th1 immune responses by inducing a death signal in the Th1 cells in order to prevent autoimmunity and undesirable immunopathology. Additionally, this interaction regulates responses that are critically important in fighting cancer. Due to its negative regulatory function on the immune system Tim-3 is classified as an immune checkpoint.
Costimulation & Immune Regulation Factors
Source:Brochure:
Immune Regulation Proteins,
T Cell Immune CheckpointsRelated to:Brands:
AdipoGen Life Sciences,
Chimerigen Laboratories, LLCProduct groups:
Proteins / Signaling MoleculesNews:
Immune Regulation Interleukins & Cytokines,
Immune Checkpoints