CD223/LAG-3
Lymphocyte-activation gene 3 (LAG-3), assigned CD223, is an immune-checkpoint receptor structurally related to CD4 but with four extracellular Ig-like domains. It is upregulated on activated CD4 and CD8 T cells, on regulatory T cells and on NK cells, where it binds MHC class II molecules and delivers inhibitory signals that attenuate TCR-driven proliferation. Additional ligands, including FGL1 and LSECtin, broaden its immunoregulatory role, and LAG-3 marks exhausted T cells in chronic infection and cancer. Blockade of LAG-3 has entered clinical oncology, and relatlimab combined with nivolumab is an approved checkpoint regimen.
