CD94 Protein, Human (HEK293, mFc)

CD94 Protein, an immune receptor crucial for self-nonself discrimination, forms a complex with KLRC1 or KLRC2 on cytotoxic and regulatory lymphocyte subsets, recognizing the non-classical major histocompatibility (MHC) class Ib molecule HLA-E loaded with self-peptides derived from the signal sequence of classical MHC class Ia and other non-classical MHC class Ib molecules. This interaction enables cytotoxic cells to monitor MHC class I expression in healthy cells, fostering self-tolerance. Primarily serving as a ligand-binding subunit without the capacity to signal, the KLRD1-KLRC1 complex acts as an immune inhibitory receptor, with CD94 playing a key inhibitory role on natural killer (NK) cells. CD94 dominantly counteracts T cell receptor signaling on a subset of memory/effector CD8-positive T cells to prevent autoimmunity. On intraepithelial CD8-positive gamma-delta regulatory T cells, CD94 triggers TGFB1 secretion, limiting the cytotoxic programming of intraepithelial CD8-positive alpha-beta T cells and distinguishing harmless from pathogenic antigens. In the HLA-E-rich tumor microenvironment, CD94 acts as an immune inhibitory checkpoint, potentially contributing to the progressive loss of effector functions in NK cells and tumor-specific T cells, a state known as cell exhaustion. Upon HLA-E-peptide binding, CD94 transmits intracellular signals through KLRC1 immunoreceptor tyrosine-based inhibition motifs (ITIMs), recruiting INPP5D/SHIP-1 and INPPL1/SHIP-2 tyrosine phosphatases to ITIMs, ultimately opposing signals from activating receptors by dephosphorylating proximal signaling molecules.