Cynomolgus Monkey LAG-3 Antibody

Applications

Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website.

Preparation and Storage

Background: LAG-3

LAG-3 (Lymphocyte activation gene-3), designated CD223, is a type I transmembrane protein that is a member of the immunoglobulin superfamily (IgSF) (1, 2). LAG ‑ 3 shares approximately 20% amino acid (aa) 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). The mature cynomolgus LAG-3 includes an extracellular domain (ECD) with four Ig-like domains, a transmembrane region and a highly charged cytoplasmic region. Within the ECD, cynomolgus LAG-3 shares 92%, 69% and 68% aa sequence identity with human, mouse and rat LAG-3, respectively. LAG-3 is expressed on activated CD4+ and CD8⁺ T cells, NK cells, and plasmacytoid dendritic cells (pDC), but not on resting T cells (1-3). LAG-3 on activated CD4⁺CD25⁺ Treg cells plays a role in their suppressive activity (4). LAG-3 limits the expansion of activated T cells and pDC in response to selected stimuli (3-5). A soluble 54 kDa form, sLAG-3, can be shed by metalloproteinases ADAM10 and TACE/ADAM17 (6, 7). While monomeric sLAG-3 itself may be inactive, shedding allows for normal T cell activation by removing negative regulation (7). Binding of sLAG-3 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 (8, 9). sLAG-3 has been used as a potential adjuvant to stimulate a cytotoxic anti-cancer immune response (9, 10). 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 (11, 12). 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 (12-14). In addition, LAG-3 is an immune checkpoint protein that modulates T-cell activation and homeostasis and is a promising target for cancer immunotherapies (15, 16).

Product Datasheets

Related Research Areas

• Co-stimulatory and Co-inhibitory Molecules
• Regulatory T Cells (Tregs)
• Search Immune Checkpoint Targets
• T Cell Antigen Recognition