Description
CD40, also known as TNFRSF5, is a 45-50 kDa type I transmembrane glycoprotein member of the TNF receptor superfamily (1). Mature human CD40 consists of a 173 amino acid (aa) extracellular domain, a transmembrane domain, and a 62 aa cytoplasmic domain (2). The extracellular domain of human CD40 shares 58% and 56% aa sequence identity with mouse and rat CD40, respectively. An antagonistic soluble human CD40 splice variant contains an alternate sequence within the extracellular and transmembrane domains and lacks a cytoplasmic domain (3). CD40 is expressed on the surface of B cells, dendritic cells, macrophages, monocytes and platelets, as well as endothelial and epithelial cells (4, 5). Interaction of CD40 with its ligand, CD40 Ligand, leads to the aggregation of CD40 molecules resulting in the initiation of bidirectional intracellular signaling in both CD40 and CD40 Ligand expressing cells (6). CD40 ligation by CD40 Ligand promotes B cell activation and T cell-dependent humoral responses (7, 8). CD40 serves multiple functions in both hematopoietic and epithelial cancers and is a target for tumor immunotherapy (9, 10). Dysregulation of CD40/CD40 Ligand expression and interactions contributes to the immune deficiency associated with HIV infection and AIDS (11, 12). It is also implicated in the pathology of multiple cardiovascular diseases including atherosclerosis, atherothrombosis, and restenosis (13, 14)