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HomeHealth articleslymphocyte surface markersWhat Are CD4 and CD8 T- Cell Surface Markers?

Lymphocyte Surface Markers

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5 min read


Marker cells are proteins that help distinguish between different types of lymphocytes and aid in their functions.

Medically reviewed by

Dr. Abdul Aziz Khan

Published At November 30, 2023
Reviewed AtNovember 30, 2023


Understanding lymphocyte surface markers is critical to working as a scientist or clinician. These molecules expressed on the outer membrane of lymphocytes provide insight into their development, function, and role in the immune system. Knowing how to identify, analyze, and interpret lymphocyte surface markers enables people to characterize different lymphocyte populations, determine their activation or differentiation state, and assess their contribution to immune responses. This article will discuss the major lymphocyte surface markers, including their properties, functions, and clinical significance. With this knowledge, people will better understand lymphocyte biology and be better equipped to study these immune cells.

What Are CD4 and CD8 T-Cell Surface Markers?

Lymphocytes, including T and B cells, are critical components of the adaptive immune system. Two of the most well-known T cell surface markers are CD4 and CD8.

  • CD4 T Cells: CD4+ T cells, also known as helper T cells. It plays a central role in the immune response. CD4+ T cells participate in activating and directing other immune cells. CD4 is a glycoprotein on the surface of helper T cells that recognizes portions of antigens presented by MHC class II molecules. The CD4 surface marker is used to identify helper T cells.

  • CD8 T Cells: CD8+ T cells, known as cytotoxic or killer T cells, directly kill the infected or abnormal cells. They recognize portions of antigens presented by MHC class I molecules. The CD8 surface marker, a glycoprotein, is used to distinguish cytotoxic T cells from other lymphocytes.

CD4 and CD8 T cell surface markers are fundamental for understanding the adaptive immune response. They signify the important functional differences between helper T cells and cytotoxic T cells. Evaluating these markers is also useful clinically when diagnosing immunodeficiency disorders and monitoring HIV progression.

Surface markers like CD4 and CD8 provide valuable insight into lymphocyte development, differentiation, and activation. Ongoing research on these and other markers is still elucidating the complexities of the immune system.

What Are B-Cell Surface Markers?

  • CD19, CD20, and CD21: B cells play an important role in the adaptive immune system. Scientists study specific proteins found on their surface to identify and characterize B cells, known as surface markers. Three of the most well-known B cell surface markers are:

  • CD19: CD19 is found in nearly all B cells and is important for B cell development, activation, and signaling. CD19 acts as a co-receptor, working with the B cell receptor (BCR) to transmit signals that regulate B cell growth, differentiation, and activation.

  • CD20: CD20 is expressed in mature B cells and some pre-B cells. It is involved in B cell activation and proliferation. CD20 is targeted by several monoclonal antibody therapies used to treat B cell lymphomas and autoimmune diseases like rheumatoid arthritis. Rituximab, a chimeric monoclonal antibody against CD20, depletes CD20-expressing B cells.

  • CD21: Also known as complement receptor 2 (CR2), CD21 binds fragments of complement component C3 and is important for B cell activation and immune complex trapping. CD21, CD19, and CD81 form a co-receptor complex that lowers the threshold for B cell activation when the BCR and CD21 are co-engaged.

In summary, CD19, CD20, and CD21 are three well-studied B cell surface markers that play important roles in B cell development, activation, proliferation, and signaling. Advancing our understanding of these markers has enabled new treatments targeting B cells in disease.

What Are NK Cell Surface Markers?

CD56 and CD16: Lymphocytes express various surface markers that can be detected using specific monoclonal antibodies. Two important surface markers for natural killer (NK) cells are:

CD56: CD56 (neural cell adhesion molecule 1 (NCAM1)) is expressed in all NK cells. It is involved in cell-cell interactions and adhesion. The density of CD56 expression correlates with the cytotoxic potential of NK cells. Dim or dull CD56 expression is associated with greater cytotoxicity.

CD16: CD16, known as FcγRIII, is the low-affinity receptor for IgG antibodies. It binds to the Fc region of IgG antibodies and mediates antibody-dependent cellular cytotoxicity (ADCC). About 90 percent of NK cells express CD16. CD16+ NK cells can directly kill antibody-coated target cells. The CD16 receptor comes in two forms:

  • CD16a (FcγRIIIa): Expressed on NK cells, macrophages, and neutrophils. It has a higher affinity for IgG1 and IgG3 antibodies.

  • CD16b (FcγRIIIb): Expressed primarily on neutrophils. It has a lower affinity for IgG antibodies compared to CD16a.

CD16 expression on NK cells can be downregulated upon activation, leading to reduced ADCC function. Certain cytokines like IL-2, IL-12, and IL-15 can upregulate CD16 expression and enhance ADCC.

CD56 and CD16 define surface markers for human NK cells. They are involved in NK cell adhesion, cytotoxicity, and ADCC function. Evaluating CD56 and CD16 expression is useful for studying NK cell biology and activity.

What Are Helper T-Cell Surface Markers?

Helper T cells, CD4+ T cells, regulate the immune system's response to foreign antigens. The presence of the CD4 surface marker characterizes them. CD4 is a glycoprotein on the surface of helper T cells that assists in recognizing MHC class II-presented antigens (APCs).

  • CD4: CD4 is a transmembrane protein co-receptor for the T cell receptor (TCR) on helper T cells. It binds to portions of the MHC class II molecule on APCs, stabilizing the interaction between the TCR and antigen-MHC complex. This binding and stabilization allow the helper T cell to become activated in response to foreign antigens presented by the APC.

Once activated, helper T cells release cytokines and other signaling molecules that activate and direct other immune cells, including:

  • Cytotoxic T cells which destroy virus-infected cells and tumor cells.

  • B cells, which produce antibodies against foreign antigens.

  • Macrophages and neutrophils eliminate pathogens and stimulate inflammation.

Without CD4, helper T cells cannot be activated, and the immune response is impaired, leading to increased susceptibility to opportunistic infections and disease. Medications that target CD4, such as entry inhibitors used to treat HIV, work by blocking the CD4 receptor and preventing the virus from entering helper T cells.

Monitoring CD4 levels is also important for assessing immune function in HIV-positive individuals. As HIV destroys helper T cells, CD4 counts progressively decrease, signaling the need to start or modify antiretroviral therapy to prevent further immune system damage. By understanding the role of CD4 and helper T cells in the immune system, clinicians can gain valuable insight into a patient's ability to fight infection and determine appropriate treatment strategies.

What Are Cytotoxic T-Cell Surface Markers?

As cytotoxic T cells mature, they develop surface markers that aid their identification and targeting abilities. The most well-known is CD8, a transmembrane glycoprotein that primarily binds to major histocompatibility complex (MHC) class I molecules. CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), play an important role in cell-mediated immunity.

CD8 surface markers are expressed as either CD8αα homodimers or CD8αβ heterodimers on mature cytotoxic T cells. These dimers bind to MHC class I molecules on antigen-presenting cells (APCs) and help stabilize the interaction between the T cell receptor (TCR) and peptide-MHC complexes. The binding of the CD8 co-receptor is required for cytotoxic T-cell activation and recognition of target cells.

Once activated, CD8+ T cells can eliminate infected or abnormal cells by releasing cytotoxic granules containing perforin and granzymes. Granzymes can enter and cause apoptosis in target cells thanks to perforin, which creates pores in the membrane. CD8+ T cells can also induce apoptosis by interacting with Fas ligand (FasL) on their surface with Fas receptors on target cells.

In addition to their cytotoxic abilities, CD8+ T cells help suppress tumor formation and eliminate infected cells with intracellular pathogens, such as viruses. They are a crucial component of the adaptive immune response against such threats.

Monitoring CD8 T cell populations and their surface markers provides insight into the status of cell-mediated immunity. Changes in the quantity of CD8+ T cells or CD8αα:CD8αβ ratio could indicate immune deficiencies or other medical conditions. Analyzing CD8+ T cell responses to specific antigens aids in diagnosing and treating various diseases and developing immunotherapies.


Lymphocyte surface markers provide critical insights into the state and function of these vital immune cells. By understanding the specific markers expressed on B cells, T cells, and natural killer cells at different stages of development and activation, researchers and clinicians gain valuable information about the immune response and health status. Though complex, the study of lymphocyte surface markers has unlocked many mysteries about how the immune system works to protect everyone.

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Dr. Abdul Aziz Khan
Dr. Abdul Aziz Khan

Medical oncology


lymphocyte surface markers
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