Lymphocyte-activation gene 3 (LAG3), also designated CD223 (cluster of differentiation 223), is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor (immunosuppressive receptor) that shows promise as a target for cancer immunotherapy.
LAG3's main ligand is MHC class II, to which it binds with higher affinity than CD4. The protein negatively regulates cellular proliferation, activation, and homeostasis of T cells, in a similar manner to CTLA-4 and PD-1.
The role of MHC II in LAG3 mediated control of immunity is highly debated. LAG3 is structurally analogous to CD4 and is believed to oppose CD4 function. However, LAG3 suppresses the function of CD8+ T cells and natural killer cells. Neither of these cell types interact with MHC II. Furthermore, the mechanism of LAG3 signaling through MHC II binding is not well understood. The cytoplasmic domain of LAG3 that mediates T cell activity through a MHC II-dependent mechanism is not thoroughly defined.
In December 2018, a research article published on Cell revealed that fibrinogen-like protein 1 (FGL1), a liver-secreted protein, is a major LAG3 functional ligand independent from MHC II. Blockade of the FGL1-LAG3 interaction by monoclonal antibodies stimulates tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand inter-dependent manner. FGL1 is highly produced by human cancer cells, and elevated FGL1 in the plasma of cancer patients is associated with a poor prognosis and resistance to anti-PD-1/B7-H1 therapy. This finding indicates the potential of LAG3 and FGL1 as drug target for cancer immunotherapies.
EUPROTEIN has developed and validated LAG3 and FGL1 proteins that could be used in the studies of the interaction between LAG3 and FGL1, pathways associated with these two proteins, and potentially drug screening. These high-quality proteins can also serve as references in immunoassay kits that quantify LAG3-FGL1 binding capabilities.
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