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B7-H2, or inducible costimulator-ligand (ICOSL), is a transmembrane, co-stimulatory ligand of the T cell-specific surface receptor Inducible T-cell costimulator (ICOS) that belongs to the B7 family and immunoglobulin superfamily, along with B7-1, B7-2, PD-L1 (B7-H1) and PD-L2. Whereas expression of inducible B7-1 and B7-2 is largely confined to specialized antigen-presenting cells of lymphoid tissues, B7-H2 expression occurs constitutively in hematopoietic and non-hematopoietic cells of peripheral organs. This striking difference in expression indicates that these three B7 ligands may enable temporally and spatially-specific regulation of T cell response through non-competitive CD28 interaction; marking a unique function of B7-H2 in immune reactions of nonlymphoid organs in which T cells have migrated to peripheral tissues having only limited expression of B7-1 and B7-2. Expression of B7-H2 has been shown to be differentially regulated by both TNF-α and IL-1β, and inducible to a lesser extent by CD40 or lipopolysaccharide stimulation. B7-H2’s binding to ICOS on activated T cells results in both positive and negative effects on immune response, including its own downregulation. As a member of the immunoglobulin superfamily, B7-H2 is crucially involved in inflammatory immune reactions and the control of excessive immune response; however, unlike B7-1 and B7-2, B7-H2 has not been shown to influence immunity through interaction with CTLA-4, and has only been shown to have restricted interaction with CD28. Interaction of B7-H2 with ICOS has been identified as a critical event in the immunosuppression of tumor-associated memory CD4+ T cells, and has been linked to various auto-immune disorders. PeproTech’s
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