Clone REAL627 recognizes the human CD223 antigen, a single-pass type I membrane protein also known as lymphocyte activation gene 3 protein (LAG-3). CD223 is a CD4 homolog with four extracellular Ig superfamily domains. Similar to CD4, CD223 oligomerizes at the surfaces of T cells and binds to MHC II on antigen presenting cells but with significantly higher affinity than CD4. CD223 is expressed on activated CD4+
T lymphocytes where it associates with the CD3–TCR complex at the cell surface and negatively regulates signal transduction. As a consequence, it negatively regulates T cell proliferation, function, and homeostasis. There is also increasing evidence of its involvement in regulatory function of tumor-infiltrated T cells in cancer, such as in Hodgkin’s lymphomas and in prostate cancer. CD223 is also expressed on activated natural killer (NK) cells, B cells, and plasmacytoid dendritic cells (pDCs).