ICOS
Function
Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response (PubMed:9930702). Upon binding to its ligand ICOSL expressed on antigen presenting cells (APCs), delivers costimulatory signals that enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines including IL10, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells (PubMed:33033255). Acts also as a costimulatory receptor critical for the differentiation of T follicular regulatory cells upon immune challenges such as viral infection (PubMed:27135603). Mechanistically, potentiates TCR-induced calcium flux by augmenting PLCG1 activation and actin remodeling (By similarity). In addition, activates PI3K signaling pathways independently of calcium flux (PubMed:30523347). Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes (By similarity).
Involvement in disease
Immunodeficiency, common variable, 1
CVID1
A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated.
Tissue Specificity
Activated T-cells. Highly expressed on tonsillar T-cells, which are closely associated with B-cells in the apical light zone of germinal centers, the site of terminal B-cell maturation. Expressed at lower levels in thymus, lung, lymph node and peripheral blood leukocytes. Expressed in the medulla of fetal and newborn thymus.
Cellular localization
- Isoform 1
- Cell membrane
- Single-pass type I membrane protein
- Isoform 2
- Secreted
Alternative names
CD278, AILIM, ICOS, Inducible T-cell costimulator, Activation-inducible lymphocyte immunomediatory molecule