CD4

CD4 is a transmembrane glycoprotein expressed primarily on the surface of T helper cells and, to a lesser extent, on other immune cells such as monocytes, macrophages, dendritic cells, and certain thymocytes. It is encoded by the CD4 gene and forms a single-pass type I membrane protein consisting of four extracellular immunoglobulin-like domains (D1–D4), a transmembrane region, and a cytoplasmic tail. The extracellular D1 domain binds to MHC class II molecules on antigen-presenting cells, helping to stabilize the interaction between the T cell receptor and peptide–MHC II and facilitating T cell activation. The cytoplasmic tail associates with the Src family kinase Lck, linking antigen recognition to intracellular signaling.

Functionally, CD4 acts as a co-receptor that enhances T cell receptor signaling and guides the development and function of CD4+ T helper cells. These cells coordinate adaptive immune responses by secreting cytokines and helping activate B cells, cytotoxic T cells, and other immune cells. CD4 is also present on various antigen-presenting cells, contributing to immune recognition and modulation.

In HIV infection, the virus uses its envelope glycoprotein gp120 to bind CD4, triggering conformational changes that permit engagement of a co-receptor (CCR5 or CXCR4). This leads to gp41-mediated fusion and viral entry, contributing to the depletion of CD4+ T cells and immunodeficiency.

Clinically, the CD4+ T cell count is a key metric in managing HIV infection and assessing immune status. Normal adult ranges are approximately 500–1500 cells per microliter. An absolute count below 200 cells/µL or a CD4 percentage below 14% is commonly used to define AIDS. CD4 is also a standard marker in flow cytometry for characterizing T-cell subsets and monitoring immune competence in other conditions.