CD223, also known as Lymphocyte Activation Gene-3 (LAG-3), is a type I transmembrane protein and a member of the immunoglobulin superfamily. It is an inhibitory immune checkpoint receptor that is selectively expressed on activated T cells, regulatory T cells, natural killer (NK) cells, and plasmacytoid dendritic cells. LAG-3 shares significant homology with CD4, particularly in its extracellular region, which contains four immunoglobulin-like domains. The molecule has a high-affinity binding to MHC class II molecules, which is its primary ligand, and this interaction negatively regulates T cell activation, proliferation, and cytokine production. Additionally, LAG-3 is involved in the negative regulation of regulatory T cell differentiation and the activation of plasmacytoid dendritic cells. In the context of cancer, LAG-3 is upregulated on tumor-infiltrating lymphocytes and is associated with tumor immune evasion, making it a promising target for cancer immunotherapy.
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