Recombinant Human LAG-3 Protein (C09-1573-626)

Protein Function:LAG-3 (Lymphocyte activation gene-3), designated CD223, is a 70 kDa type I transmembrane protein that is a member of the immunoglobulin superfamily (IgSF). LAG-3 shares approximately 20% amino acid sequence homology with CD4, but has similar structure and binds to MHC class II with higher affinity, providing negative regulation of T cell receptor signaling. Human LAG-3 cDNA encodes 525 amino acids (aa) that include a 28 aa signal sequence, a 422 aa extracellular domain (ECD) with four Ig-like domains, a transmembrane region and a highly charged cytoplasmic region. Within the ECD, human LAG-3 shares sequence identity with mouse, rat, porcine, and bovine LAG-3. LAG-3 is expressed on activated CD4+ and CD8+ T cells, NK cells, and plasmacytoid dendritic cells (pDC), but not on resting T cells. LAG-3 on activated CD4+CD25+ Treg cells plays a role in their suppressive activity. LAG-3 limits the expansion of activated T cells and pDC in response to selected stimuli. A soluble 54 kDa form, sLAG-3, can be shed by metalloproteinases ADAM10 and TACE/ADAM17. While monomeric sLAG-3 itself may be inactive, shedding allows for normal T cell activation by removing negative regulation. Binding of a homodimerized sLAG-3/Ig fusion protein to MHC class II molecules induces maturation of immature DC, and secretion of cytokines such as IFN-gamma and TNF-alpha by type 1 cytotoxic CD8+ T cells and NK cells. sLAG-3/Ig has been used as a potential adjuvant to stimulate a cytotoxic anti-cancer immune response. In mice, deletion of LAG-3 and another negative regulator, PD-1, facilitates anti-cancer response but also blocks self-tolerance and increases susceptibility to autoimmune diseases. In humans, antibody-mediated down regulation of LAG-3 and PD-1 allows more effective control of chronic malaria, while in NOD (non obese diabetic) mice, deletion of LAG-3 alone accelerates diabetes. LAG-3 is an immune checkpoint protein that modulates T-cell activation and homeostasis and is a promising target for cancer immunotherapy. Specification: ActiBioPure™, Bioactive, Animal Free, Carrier Free, ≥95%(SDS-PAGE)