LAG-3, Fc Chimera, Recombinant, Mouse (CD223, Lymphocyte Activation Gene-3)

LAG­3 (Lymphocyte activation gene­3), designated CD223, is a 70kD type I transmembrane protein that is a member of the immunoglobulin superfamily (IgSF) (1, 2). LAG­3 shares ~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 (1, 2). Mouse LAG-3 cDNA encodes 521 amino acids (aa) that include a 22aa signal sequence, a 420aa extracellular domain (ECD) with four Ig­like domains, a transmembrane region and a highly charged cytoplasmic region. Within the ECD, mouse LAG­3 shares 86% aa sequence identity with rat LAG­3, and 65-69% with human, porcine, and bovine LAG­3. LAG­3 is expressed on activated CD4+ and CD8+ T cells, NK cells, and plasmacytoid dendritic cells (pDC), but not on resting T cells (1­3). LAG­3 on activated CD4+CD25+ Treg cells plays a role in their suppressive activity (4). LAG­3 limits the expansion of activated T cells and pDC in response to selected stimuli (3­5). A soluble 54kD form, sLAG-3, can be shed by metalloproteinases ADAM10 and TACE/ADAM17 (6, 7). While monomeric sLAG­3 itself may be inactive, shedding allows for normal T cell activation by removing negative regulation (7). 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 IFN­gamma and TNF­alpha by type 1 cytotoxic CD8+ T cells and NK cells (8, 9). sLAG-3/Ig has been used as a potential adjuvant to stimulate a cytotoxic anti-cancer immune response (9, 10). In mice, deletion of LAG­3 and another negative regulator, PD-1, facilitates anti-cancer response but also blocks self­tolerance and increases susceptibility to autoimmune diseases (11, 12). In humans, antibody-mediated down-regulation of LAG­3 and PD­1 allows more effective control of chronic malaria, while in NOD (non­obese diabetic) mice, deletion of LAG­3 alone accelerates diabetes (12-14). Source: Recombinant protein corresponding to mouse LAG-3 Fc Chimera, CF. Molecular Weight: ~85-100kD, Endotoxin: <0.10EU/1ug (LAL method), Storage and Stability: Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute in sterile dPBS. Aliquot to avoid repeated freezing and thawing. Store at -20°C. Reconstituted product is stable for 12 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.