T cell surface glycoprotein CD4 (CD4)

CD4 is a type I transmembrane glycoprotein found primarily on the surface of helper T lymphocytes but also present on monocytes, macrophages, dendritic cells, B cells, granulocytes, and certain brain regions. It acts as a co-receptor alongside the T-cell receptor (TCR), specifically recognizing antigens presented by major histocompatibility complex class II molecules. Structurally, it consists of four extracellular immunoglobulin-like domains connected to a short stalk region that traverses the membrane and ends with a cytoplasmic tail capable of recruiting Lck tyrosine kinase. This recruitment is essential for initiating intracellular signaling cascades that drive lymphokine production and full activation/motility/adhesion responses in helper T-cells. Beyond its physiological role in adaptive immunity—where it orchestrates cellular responses against pathogens—CD4 serves as the principal high-affinity cellular entry receptor for human immunodeficiency virus type 1 (HIV), making it central both to normal immune function and pathogenesis in diseases such as AIDS. Therapeutically relevant drugs target this molecule either to modulate immune activity or prevent viral entry.

Other names

Cluster of differentiation 4T helper cell antigenLeu-3T4 (historical)OKT4 antigen

Monoclonal antibodies can block or modulate CD4 function or deplete CD4+ cells. Inhibition of HIV entry by blocking gp120 binding site on CD4. Modulation of immune responses via interference with coreceptor function.