CD4

CD4 correceptor

CD4 receptor

CD4 and LAG-3 with opposing functions

Reference ranges for blood tests - white blood cells

File:CD4-R113-5ug-tonsil.png

CD4-R113-5ug-tonsil

CD4 is a glycoprotein found on the surface of immune system cells such as T helper cells, monocytes, macrophages, and dendritic cells. It is a member of the immunoglobulin superfamily and plays a critical role in the immune response. CD4 acts as a co-receptor in the T cell receptor (TCR) signaling pathway by binding to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APCs). This interaction is crucial for the activation of T helper cells, which in turn help activate other immune cells, leading to a coordinated response against pathogens.

Structure and Function

The CD4 molecule is composed of four extracellular immunoglobulin-like domains (D1 to D4), a transmembrane domain, and a cytoplasmic tail. The D1 domain is primarily involved in binding to the MHC class II molecule. The cytoplasmic tail of CD4 interacts with lymphocyte-specific protein tyrosine kinase (Lck), which is essential for the initiation of TCR signaling.

Upon engagement with MHC class II, CD4 facilitates the recruitment of Lck to the TCR complex, leading to the phosphorylation and activation of downstream signaling molecules. This results in T cell activation, proliferation, and differentiation into effector cells that can produce various cytokines to regulate the immune response.

Role in HIV Infection

CD4 is also known for its role as the primary receptor for the Human Immunodeficiency Virus (HIV). HIV binds to CD4 in conjunction with a co-receptor (either CCR5 or CXCR4) to enter and infect T helper cells. This interaction is a critical step in the HIV life cycle and has made CD4 a significant target for HIV research and therapeutic intervention. The depletion of CD4+ T cells is a hallmark of AIDS (Acquired Immunodeficiency Syndrome), leading to the progressive failure of the immune system.

Clinical Significance

The CD4 count is a key marker used in the clinical management of HIV/AIDS. It measures the number of CD4+ T cells in a cubic millimeter of blood, providing an indication of the health of a person's immune system. Antiretroviral therapy (ART) aims to suppress HIV replication, which helps to increase or maintain CD4 counts at a level that minimizes the risk of opportunistic infections and other AIDS-related conditions.

Research and Therapeutics

Research into CD4 has led to the development of several therapeutic strategies targeting CD4+ T cells. These include monoclonal antibodies that block the interaction between CD4 and MHC class II to modulate the immune response in autoimmune diseases, as well as strategies to enhance CD4+ T cell responses in vaccines and cancer immunotherapy.

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