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). 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. 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 limits the expansion of activated T cells and pDC in response to selected stimuli. LAG-3 is an immune checkpoint protein that modulates T-cell activation and homeostasis and is a promising target for cancer immunotherapy (1-5).
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