Human Lymphocyte activation gene 3 protein( LAG3) is a member of immunoglobulin (Ig) superfamily. LAG3 contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. LAG3 is involved in lymphocyte activation and can bind to HLA class-II antigens. It is selectively expressed in activated T and NK cells. LAG3 has a negative regulatory function in T cells and acts as as a new marker of T cell induced B cell activation. As a soluble molecule; LAG3 activates antigen-presenting cells through MHC class II signaling. It can lead to increased antigen-specific T-cell responses in vivo. LAG-3 has higher affinity to MHC class II than CD4.
Human Lymphocyte activation gene 3 protein( LAG3) is a member of immunoglobulin (Ig) superfamily. LAG3 contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. LAG3 is involved in lymphocyte activation and can bind to HLA class-II antigens. It is selectively expressed in activated T and NK cells. LAG3 has a negative regulatory function in T cells and acts as as a new marker of T cell induced B cell activation. As a soluble molecule, LAG3 activates antigen-presenting cells through MHC class II signaling. It can lead to increased antigen-specific T-cell responses in vivo. LAG-3 has higher affinity to MHC class II than CD4.
Leukocyte associated Ig-like receptor-1 (LAIR1) is a surface molecule expressed on human mononuclear leukocytes that functions as an inhibitory receptor on human NK cells. In addition to NK cells, LAIR1 is expressed on T cells, B cells, macrophages, and dendritic cells. It is predicted to mediate inhibitory functions based on the presence of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic domain. Cross-linking of LAIR1 on human T cell clones results in inhibition of cytotoxicity only in T cell clones that lack CD28 and are able to spontaneously lyse certain targets in vitro. Moreover, the cytolytic activity of freshly isolated T cells, which is thought to be mainly due to "effector" T cells, can be inhibited by anti-LAIR1 mAb. Thus, LAIR1 functions as an inhibitory receptor not only on NK cells, but also on human T cells. This indicates that LAIR1 provides a mechanism of regulation of effector T cells and may play a role in the inhibition of unwanted bystander responses mediated by Ag-specific T cells.
Leukocyte-Associated Immunoglobulin-Like Receptor 1 (LAIR1) is a single-pass type I membrane protein. LAIR1 expressed on the majority of peripheral mononuclear cells, including natural killer (NK) cells, T-cells, B-cells, monocytes, and dendritic cells, highly in naive T-cells and B-cells. As an inhibitory receptor, LAIR1 plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. LAIR1 plays inhibitory role independently of SH2-containing phosphatases and modulates cytokine production in CD4+ T-cells. It down-regulates IL2 and IFNG production while inducing secretion of transforming growth factor beta, also down-regulates IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. LAIR1 inhibits the differentiation of peripheral blood precursors towards dendritic cells. It also restrains proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells.
Leukocyte-associated immunoglobulin-like receptor 2 ( LAIR2 ), also known as CD306, is a 131 amino acid protein containing one lg-like C2-type domain. It is expressed as a soluble receptor exhibiting high affinity for various collagen molecules to which it binds in a hydroxyproline-dependent manner. LAIR2 is a member of the immunoglobulin superfamily and was identified by its similarity to LAIR1, an inhibitory receptor present on mononuclear leukocytes. LAIR2 is thought to be secreted and may help modulate mucosal tolerance. As a natural competitor for LAIR1, soluble LAIR2 prevents binding of human LAIR1 to collagens and LAIR1 cross-linking, thereby regulating its inhibitory potential. Accordingly, LAIR2 is suggested to perform an immunoregulatory function.
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