Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation. Exists as a GPI-anchored and as a transmembrane form, each likely initiating distinct signaling pathways via phosphoinositol 3-kinase in activated NK cells and via LCK and CD247/CD3 zeta chain in activated T cells (PubMed:19109136, PubMed:11978774, PubMed:17307798). Receptor for both classical and non-classical MHC class I molecules (PubMed:9973372, PubMed:12486241). In the context of acute viral infection, recognizes HLA-C and triggers NK cell cytotoxic activity, likely playing a role in anti-viral innate immune response (PubMed:12486241). On CD8+ T cells, binds HLA-A2-B2M in complex with a viral peptide and provides a costimulatory signal to activated/memory T cells (PubMed:9973372). Upon persistent antigen stimulation, such as occurs during chronic viral infection, may progressively inhibit TCR signaling in memory CD8+ T cells, contributing to T cell exhaustion (PubMed:25255144). On endothelial cells, recognizes HLA-G and controls angiogenesis in immune privileged sites (PubMed:16809620). Receptor or ligand for TNF superfamily member TNFRSF14, participating in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. Upon ligation of TNFRSF14, provides stimulatory signal to NK cells enhancing IFNG production and anti-tumor immune response (By similarity). On activated CD4+ T cells, interacts with TNFRSF14 and down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (PubMed:18193050). In the context of bacterial infection, acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and pro-inflammatory cytokines (By similarity). The soluble GPI-cleaved form, usually released by activated lymphocytes, might play an immune regulatory role by limiting lymphocyte effector functions. Homomultimer; disulfide-linked (Probable). Interacts with HLA-G (PubMed:16809620). Interacts with HLA-A2-B2M in complex with an HIV-derived peptide (PubMed:9973372). Interacts with TNFRSF14 (via cysteine-rich domain 1); this interaction is direct (PubMed:18193050). Interacts with LCK and CD247/CD3 zeta chain (PubMed:11978774). Released from the cell membrane by GPI cleavage. Expression is restricted to functional NK and cytotoxic T lymphocytes. Expressed in viral-specific effector memory and terminally differentiated effector memory CD8+ T cells. Expressed in memory and activated CD4+ T cell subsets (at protein level) (PubMed:9743336, PubMed:18193050, PubMed:11978774, PubMed:25255144). Expressed at high levels in intraepithelial lymphocytes (at protein level) (PubMed:9743336). Expressed in both alpha-beta and gamma-delta CD8+ T cell subsets (at protein level) (PubMed:9743336, PubMed:18193050, PubMed:11978774). Expressed in umbilical vein endothelial cells (at protein level) (PubMed:16809620). Expressed in monocytes and at lower levels in B cells (PubMed:23761635). Isoform 3: Expressed exclusively in activated NK cells (at protein level) (PubMed:19109136). Up-regulated on CD4+ T cells upon stimulation via T cell receptor plus costimulation via CD28 (PubMed:18193050). Up-regulated by IL15 on immunoregulatory NCAM1/CD56-bright NK cells (PubMed:17237375). Mutagenesis of TYR-225 to Phe abolishes intracellular signaling.