CD160
Description
The CD160 (CD160 molecule) is a protein-coding gene located on chromosome 1.
CD160 antigen is a protein that in humans is encoded by the CD160 gene. CD160 is a 27 kDa glycoprotein which was initially identified with the monoclonal antibody BY55. Its expression is tightly associated with peripheral blood NK cells and CD8 T lymphocytes with cytolytic effector activity. The cDNA sequence of CD160 predicts a cysteine-rich, glycosylphosphatidylinositol-anchored protein of 181 amino acids with a single Ig-like domain weakly homologous to KIR2DL4 molecule. CD160 is expressed at the cell surface as a tightly disulfide-linked multimer. RNA blot analysis revealed CD160 mRNAs of 1.5 and 1.6 kb whose expression was highly restricted to circulating NK and T cells, spleen and small intestine. Within NK cells CD160 is expressed by CD56dimCD16+ cells whereas among circulating T cells its expression is mainly restricted to TCRgd bearing cells and to TCRab+CD8brightCD95+CD56+CD28-CD27-cells. In tissues, CD160 is expressed on all intestinal intraepithelial lymphocytes. CD160 shows a broad specificity for binding to both classical and nonclassical MHC class I molecules.
== Clinical significance == CD160 is a ligand for HVEM, and considered a proposed immune checkpoint inhibitor with anti-cancer activity along with anti- PD-1 antibodies.
CD160 is a receptor found on immune cells, capable of delivering both stimulatory and inhibitory signals that influence cell activation and differentiation. It exists in two forms, a GPI-anchored form and a transmembrane form, each likely triggering distinct signaling pathways. The GPI-anchored form utilizes phosphoinositol 3-kinase in activated NK cells, while the transmembrane form utilizes LCK and CD247/CD3 zeta chain in activated T cells. CD160 serves as a receptor for both classical and non-classical MHC class I molecules. In acute viral infections, it recognizes HLA-C and activates NK cell cytotoxicity, contributing to the antiviral innate immune response. On CD8+ T cells, CD160 binds to HLA-A2-B2M complexed with viral peptides, providing a costimulatory signal to activated/memory T cells. However, during persistent antigen stimulation, such as chronic viral infection, CD160 may progressively inhibit TCR signaling in memory CD8+ T cells, contributing to T cell exhaustion. CD160 also interacts with HLA-G on endothelial cells, regulating angiogenesis in immune privileged sites. CD160 is either a receptor or a ligand for TNFRSF14, a member of the TNF superfamily, and participates in bidirectional cell-cell signaling between antigen presenting cells and lymphocytes. When TNFRSF14 is engaged, CD160 activates NK cells, enhancing IFNG production and anti-tumor immunity. In activated CD4+ T cells, CD160 interacts with TNFRSF14 to down-regulate CD28 costimulatory signaling, limiting memory and alloantigen-specific immune responses. During bacterial infection, CD160 acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and pro-inflammatory cytokines. The soluble, GPI-cleaved form of CD160, typically released by activated lymphocytes, may play a regulatory role in the immune system by limiting lymphocyte effector functions.
CD160 is also known as BY55, NK1, NK28.
