CD4 is expressed on the surface of specific immune cells, mostly T cells, though there are other types of CD4+ immune cells. T cells are a type of lymphocyte, which is a type of white blood cell. White blood cells play a critical role in immune response, and unlike red blood cells, lymphocytes do not transport oxygen through the body. Both red and white blood cells are originally formed from hematopoietic stem cells located in the bone marrow, the soft internal region of the bone that supports cellular growth and replenishment. Hematopoietic stem cells reproduce and differentiate into several different cell types, including lymphocytes. Stem cells differentiate into B cells or T cells, and T cells are able to migrate to the thymus as part of their maturation. B and T cells are each capable of interacting with foreign molecules in the body, and stimulating a response that will help remove them. Molecules that trigger a response from a B or T cell are called antigens, and antigens are often proteins encoded by non-human genomes. When a human protein receptor on a lymphocyte binds to an antigen, the immune cell triggers an immune response. In this way, antigens encoded by viruses or bacteria can be identified, targeted, and destroyed by our immune system.

Collectively, a person’s population of B and T cells can interact with a vast variety of antigens. However, any given B cell or T cell produces many copies of only one type of specific antigen receptor, each of which can bind to only one specific type of antigen. When an individual B cell physically binds to its antigen, the B cell rapidly produces more receptor-like molecules that are secreted from the B cell into the fluids of the body. These secreted versions of the receptors are called antibodies (Ab) or immunoglobulins (Ig), which can bind to the same antigen type. B cells allow the immune system to recognize antigens in the fluids of the body because B cells produce antibodies that circulate in our blood and lymph where they can bind to antigens and target them for removal by an efficient immune response. Frequently, scientists isolate antibodies as treatment for disease because these proteins bind tightly to specific proteins of a pathogen and target that pathogen for destruction. Antibodies can also be used as diagnostic tools, since the presence of a pathogen in a patient can be detected when the patient’s antibodies bind very tightly to it. Some forms of tests for HIV infection make use of a patient’s antibodies in this way.

T cells do not secrete their antigen receptor, nor do they make antibodies. T cells receptors are activated by antigens that are displayed on the surface of particular types of cells that use a set of proteins called the major histocompatibility complex (MHC), also in humans referred to as human leukocyte antigen (HLA). Most cells in our body, with the exception of red blood cells, display MHC class I (MHC I) on their surfaces. Specialized lymphocytes produce MHC class II (MHC II) proteins on their surfaces. These MHC protein complexes function as an antigen-presenting system for T cells and their receptors. Generally, MHC I molecules display small segments of proteins (called peptides) that are translated in the same cell that displays the peptide. MHC II molecules display peptides that were originally produced outside the cell displaying it. For example, a host cell such as a macrophage might engulf an invading pathogenic bacterium in order to kill the invading cell. Protein components of the bacteria are bound by MHC II, and moved to the surface of the macrophage so that the captured bacterial protein antigen is “presented” on the outside of the macrophage. When the bacterial antigen peptide is displayed on the surface of a cell by an MHC II molecule, a T cell receptor on the surface of the T cell might be able to recognize and bind to the antigen/MHC complex on the surface of an antigen-presenting cell. The CD4 protein displayed on the surface of T cells helps the T cell receptor bind to antigen presented with MHC II. CD4 also binds directly to antigen presented by MHC II molecules. If the population of CD4+ T cells drops in the body, the immune system is crippled in its ability to recognize antigen-presenting cells, and therefore is crippled in its ability to mount a vigorous immune response triggered by pathogenic antigens.

To summarize, when a T cell receptor interacts with an MHC plus peptide, the T cell receptor activates its T cell and initiates an immune response. The type of response depends on the type of T cell (and cognate MHC type) involved. CD4+ cells capable of being infected by HIV include helper T cells, monocytes, macrophages, and dendritic cells. Helper T cells recognize MHC II plus antigen, whereas cytotoxic T cells (also called CD8+ cells) recognize MHC class I plus antigen. Helper T cells produce cytokines, molecules that are secreted from the cell to stimulate other immune cells, such as B cells. In this way, appropriate B cell function requires a healthy population of CD4+ T cells. When HIV infects and impairs the function of CD4+ cells, it broadly limits the immune system. People with reduced numbers of CD4+ cells have weakened response to infections which can lead to opportunistic infections and cancers that normally are eliminated by a healthy and vigorous immune system.