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ICOSLG
ICOS ligand is a protein that in humans is encoded by the ICOSLG gene located at chromosome 21. ICOSLG has also been designated as CD275 (cluster of differentiation 275).
ICOSLG is glycosylated transmembrane structure, which is classified as a member of the B7 family due to the significant homology with B7 family members. The B7/CD28 superfamily provides both positive and negative co-signals to immunocytes in immune responses.
The interaction of ICOSLG with ICOS, the specific receptor for ICOSLG, is critically involved in the activation, proliferation, differentiation and cytokine production of T cells as well as in the antibody secretion from B cells during secondary immune responses.
ICOSLG, which is extensively expressed in both non-lymphatic and lymphatic tissues, is an important molecule in upregulating and promoting T cell immune responses. Expression of ICOSLG in naive B cells and monocytes in PBMCs is at a low level. After stimulation by IFN-γ, TNF-α, or LPS, it can be quickly up-regulated. The induced expression of ICOS on activated T cells mainly regulates the secretion of Th2 cytokines and thus shifts the immune response to the Th2 type. It has been reported that the ICOS/ICOSLG pathway is involved in immunopathogenesis such as infection, hypersensitivity, autoimmune diseases, transplantation immunity and tumor immunity.
ICOSLG is also a major costimulator in endothelial cell-mediated T cell activation. It has an important physiological role of ICOSLG in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue.
Inducible costimulator-ligand (ICOS-L) is a member of the B7 family of costimulatory ligands sharing 19–20% sequence identity with CD80 and CD86. Two splice variants of human ICOSLG have been described and designated hICOSLG and B7-H2/B7RP-1/hLICOS.
Both molecules have an identical extracellular domain but differ at the carboxyl-terminal end of their cytoplasmic regions. In humans, cell surface expression of ICOSLG has been described on B cells, dendritic cells, monocytes/macrophages, and T cells. In addition, mRNA expression of ICOSLG has been detected in a variety of lymphoid and nonlymphoid organs, with hICOSLG showing a more lymphoid-restricted expression pattern (spleen, lymph node), whereas B7-H2/B7RP-1/hLICOSmRNA was expressed in all organs examined (e.g., spleen, kidney, heart, and brain).
Murine ICOSLG, unlike CD80 and CD86, does not interact with CD28 or CTLA-4 (CD152). Instead, ICOSLG binds to ICOS, a T cell-specific costimulatory molecule homologous to CD28 and CTLA-4. In humans, ICOSLG binds to ICOS but also to CD28 and CTLA-4.
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ICOSLG
ICOS ligand is a protein that in humans is encoded by the ICOSLG gene located at chromosome 21. ICOSLG has also been designated as CD275 (cluster of differentiation 275).
ICOSLG is glycosylated transmembrane structure, which is classified as a member of the B7 family due to the significant homology with B7 family members. The B7/CD28 superfamily provides both positive and negative co-signals to immunocytes in immune responses.
The interaction of ICOSLG with ICOS, the specific receptor for ICOSLG, is critically involved in the activation, proliferation, differentiation and cytokine production of T cells as well as in the antibody secretion from B cells during secondary immune responses.
ICOSLG, which is extensively expressed in both non-lymphatic and lymphatic tissues, is an important molecule in upregulating and promoting T cell immune responses. Expression of ICOSLG in naive B cells and monocytes in PBMCs is at a low level. After stimulation by IFN-γ, TNF-α, or LPS, it can be quickly up-regulated. The induced expression of ICOS on activated T cells mainly regulates the secretion of Th2 cytokines and thus shifts the immune response to the Th2 type. It has been reported that the ICOS/ICOSLG pathway is involved in immunopathogenesis such as infection, hypersensitivity, autoimmune diseases, transplantation immunity and tumor immunity.
ICOSLG is also a major costimulator in endothelial cell-mediated T cell activation. It has an important physiological role of ICOSLG in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue.
Inducible costimulator-ligand (ICOS-L) is a member of the B7 family of costimulatory ligands sharing 19–20% sequence identity with CD80 and CD86. Two splice variants of human ICOSLG have been described and designated hICOSLG and B7-H2/B7RP-1/hLICOS.
Both molecules have an identical extracellular domain but differ at the carboxyl-terminal end of their cytoplasmic regions. In humans, cell surface expression of ICOSLG has been described on B cells, dendritic cells, monocytes/macrophages, and T cells. In addition, mRNA expression of ICOSLG has been detected in a variety of lymphoid and nonlymphoid organs, with hICOSLG showing a more lymphoid-restricted expression pattern (spleen, lymph node), whereas B7-H2/B7RP-1/hLICOSmRNA was expressed in all organs examined (e.g., spleen, kidney, heart, and brain).
Murine ICOSLG, unlike CD80 and CD86, does not interact with CD28 or CTLA-4 (CD152). Instead, ICOSLG binds to ICOS, a T cell-specific costimulatory molecule homologous to CD28 and CTLA-4. In humans, ICOSLG binds to ICOS but also to CD28 and CTLA-4.