CD4

What is CD4 protein?

CD4 gene (CD4 molecule) is a protein coding gene which situated on the long arm of chromosome 12 at locus 12p13. This gene encodes the CD4 membrane glycoprotein of T lymphocytes. The CD4 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class II MHC molecules. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, granulocytes, as well as in various regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. The CD4 protein is consisted of 458 amino acids and CD4 molecular weight is approximately 51.1 kDa.

What is the function of CD4 protein?

CD4 protein is a key immunomodulatory molecule, mainly expressed on the surface of helper T cells. It acts as a co-receptor of T cell receptors and binds to MHC Class II molecules to help T cells recognize antigens presented by antigen-presenting cells, activate T cells and trigger immune responses. CD4 proteins play a critical role in T cell activation, proliferation, and differentiation, influencing cytokine production, cell adhesion and migration, and differentiation of T cell subsets such as Th1, Th2, Th17, and Treg, which perform different but important functions in regulating immune response and maintaining immune balance. In addition, CD4 protein is also involved in the infection mechanism of HIV virus, HIV uses CD4 protein as the main receptor to enter the host cell.

Fig1. Influence of distinct cytokine milieu in the differentiation of CD4+T cells. (Rishi Vishal Luckheeram, 2012)

CD4 related signaling pathway

As co-receptors on the surface of T cells, CD4 works with T cell receptors (TCRS) to recognize antigens presented by antigen-presenting cells (APCs) via MHC Class II molecules, a process that activates T cells and triggers downstream signaling molecules including tyrosine kinase Lck. These signaling events activate a variety of intracellular signaling pathways, such as Ras-MAPK, PI3K-Akt, and calmodulin pathways, leading to altered gene expression, cytokine production, cell proliferation and differentiation, and T cell migration and adhesion. CD4 protein is also closely related to HIV infection, as the main receptor for the HIV virus to enter the host cell, CD4 binds to the gp120 protein on the surface of the virus, promoting the internalization and infection of the virus. In addition, the activation and differentiation of CD4-positive T cells are also influenced by the environment of cytokines, such as IL-12, IL-4, IL-6, and TGF-β, which guide T cells to differentiate into different effecting and regulatory subsets, such as Th1, Th2, Th17, and Treg, through specific signaling pathways. These subgroups play a key role in adaptive immune responses.

CD4 related diseases

CD4-related diseases refer to a group of conditions that affect the immune system, specifically the CD4+ T cells. These cells play a crucial role in regulating the immune response and protecting the body from infections. CD4-related diseases include HIV/AIDS, which is caused by the human immunodeficiency virus (HIV) that attacks and destroys CD4+ T cells, leading to a weakened immune system. Other CD4-related diseases may include autoimmune disorders, such as lupus and rheumatoid arthritis, which are characterized by an overactive immune response that attacks healthy tissues. Treatment for CD4-related diseases often involves managing symptoms and preventing further damage to the immune system.

Bioapplications of CD4

By altering the structure of the HIV-1 envelope protein so that it can bind rhCD4 more efficiently, the ability of SHIV (simian human immunodeficiency virus) to replicate in Rhesus monkey lymphocytes can be improved, which has important implications for studying the transmission of HIV-1 and the testing of vaccines. In addition, rhCD4 protein is also used in the development of immunotherapy, especially in tumor immunotherapy, by activating CD4+ T cells to enhance the body's anti-tumor immune response. CD4+ T cells can not only assist CD8+ T cells to play cytotoxic roles, but also have the ability to directly kill tumor cells, which provides a new strategy and target for cancer treatment.