The CD4 protein is an important component of the human immune system. It is a glycoprotein found on the surface of specific immune cells. Understanding CD4 helps explain how the body fights disease and how pathogens, like HIV, can compromise these defenses.
What the CD4 Protein Is
The CD4 protein is a transmembrane glycoprotein, spanning the cell membrane. It is primarily located on the surface of helper T lymphocytes, also known as CD4+ T cells, which are a major component of the adaptive immune system.
CD4 is also present on the surface of other immune cells, including monocytes, macrophages, and dendritic cells. Structurally, CD4 is part of the immunoglobulin superfamily and contains four immunoglobulin domains (D1 to D4) exposed on the cell’s outer surface. The D1 domain interacts with Major Histocompatibility Complex (MHC) class II molecules, which is important for its function.
CD4’s Role in Immune Function
CD4 functions as a co-receptor for the T cell receptor (TCR). It assists the TCR in binding to Major Histocompatibility Complex (MHC) Class II molecules, presented by antigen-presenting cells (APCs). The extracellular D1 domain of CD4 specifically binds to the β2 region of MHC class II. This close proximity allows for the activation of the tyrosine kinase Lck, which amplifies the signal generated by the TCR.
This interaction between the TCR, CD4, and MHC Class II molecules is an important step for the activation of helper T cells. Once activated, helper T cells differentiate into various subtypes, such as Th1, Th2, and Th17 cells, each with specialized responses. These activated helper T cells then orchestrate a broader immune response by activating other immune cells, including B cells to produce antibodies and cytotoxic T cells to eliminate infected cells.
CD4 and HIV Infection
The CD4 protein serves as the main entry point for the Human Immunodeficiency Virus (HIV) to enter human immune cells. The initial step involves the binding of the HIV envelope glycoprotein gp120 to the CD4 protein on the surface of target cells, particularly helper T cells.
Following the binding of gp120 to CD4, the gp120 protein undergoes conformational changes. These changes allow gp120 to interact with chemokine co-receptors, most commonly CCR5 or CXCR4, also located on the cell surface. This co-receptor binding is important as it stabilizes viral attachment and brings the viral and host cell membranes into close proximity. This interaction triggers the exposure of another viral envelope protein, gp41, which mediates the fusion of the viral and cellular membranes, allowing the viral contents to enter the host cell. This infection and destruction of CD4+ T cells by HIV leads to immunodeficiency and the development of Acquired Immunodeficiency Syndrome (AIDS).
Interpreting CD4 Levels
A CD4 count measures the number of CD4+ T cells in a cubic millimeter of blood. This count is an important indicator of overall immune system health, particularly for individuals with HIV infection. Healthcare providers use CD4 counts to monitor disease progression, assess the effectiveness of antiretroviral therapy (ART), and determine the risk of developing opportunistic infections.
A normal CD4 count ranges from 500 to 1,400 cells per cubic millimeter of blood. In the context of HIV, a CD4 count below 200 cells per cubic millimeter is a diagnostic criterion for AIDS and indicates an increased risk for life-threatening infections. While a single count can provide information, the trend of CD4 levels over time is more informative than a single measurement. Effective ART aims to reduce the viral load, which allows CD4 counts to increase, improving the immune system’s ability to fight infections.