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 ( ). Receptor for both classical and non-classical MHC class I molecules (, ). 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 . On CD8+ T cells, binds HLA-A2-B2M in complex with a viral peptide and provides a costimulatory signal to activated/memory T cells . 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 . On endothelial cells, recognizes HLA-G and controls angiogenesis in immune privileged sites . 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 . 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.
Subcellular locations: Cell membrane
Subcellular locations: Secreted
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) ( , ). Expressed at high levels in intraepithelial lymphocytes (at protein level) . Expressed in both alpha-beta and gamma-delta CD8+ T cell subsets (at protein level) ( ). Expressed in umbilical vein endothelial cells (at protein level) . Expressed in monocytes and at lower levels in B cells . Isoform 3: Expressed exclusively in activated NK cells (at protein level) .