CD4 Receptor: Structure, Immune Function, and Disease Roles

I. Structural Characteristics and Cellular Distribution

The CD4 receptor is a single-chain glycoprotein composed of four extracellular immunoglobulin-like domains (D1–D4), a transmembrane region, and a short cytoplasmic tail. This specific organization allows CD4 to interact precisely with major histocompatibility complex class II (MHC II) molecules.

II. Antigen Recognition and T Cell Activation

CD4 acts as a bridge during immune signaling. When an APC presents a peptide fragment via MHC II, the T cell receptor (TCR) binds to it. CD4 simultaneously binds to the non-polymorphic regions of the MHC II, stabilizing the interaction.

This dual recognition enhances signal strength and specificity, facilitated by the cytoplasmic association with the Src-family kinase Lck, which triggers the necessary signaling cascades for cell proliferation.

III. Role in Immune Regulation

Activated CD4⁺ T cells differentiate into distinct subsets—Th1, Th2, Th17, and Tregs—secreting cytokines like IL-2 and IFN-γ. These signals coordinate:

IV. CD4 in Disease Pathogenesis

HIV and AIDS

CD4 is the primary "gateway" for HIV. The viral envelope glycoprotein gp120 binds to CD4, enabling viral entry. The subsequent depletion of CD4⁺ T cells leads to the profound immune suppression characteristic of AIDS.

Autoimmunity

Dysregulation here can be catastrophic. If CD4⁺ cells lose self-tolerance, they drive inappropriate cytokine production and immune-mediated tissue damage in various inflammatory disorders.