Decoding Cell Surface Markers: Key Tools for Understanding Cellular Communication

Cell surface markers, also known as cell surface antigens, are proteins or glycoproteins expressed on the surface of cells. These markers play a critical role in cellular communication, signaling, and immune response. Understanding and identifying these markers is fundamental to cell biology and immunology research. In this blog post, we will delve into the technical aspects of cell surface markers and the use of specific antibodies to study these crucial components.

 Quantification of immune cells and cell-surface markers measured in the Milieu Intérieur cohort. Strategy: flow cytometry was used to quantify (as MFI) the expression of phenotypic markers of differentiation or activation in cells of various lineages or differentiation states (interconnecting lines), as well as to quantify the cells themselves, for the identification of immunophenotypes significantly associated with non-genetic or genetic factors (key); numbers in parentheses (bottom left corners) indicate eight-color panels performed, grouped on the basis of cellular lineage (Supplementary Figs. 1-10 and Supplementary Tables 2 and 3). ILC1, ILC2 and ILC3, subsets of ILCs; T CM cells, central memory T cells; T EM cells, effector memory T cells; T FH , T H 1, T H 17 and T H 2, subsets of helper T cells; NKp46, activating receptor; ICOS, costimulatory receptor.

The Importance of Cell Surface Markers

Cell surface markers serve as identification tags that allow cells to communicate and interact with each other. They are involved in a variety of cellular processes including:

  1. Immune Response: The immune response relies heavily on cell surface markers for its key functions. These markers are crucial for the initial recognition of antigens by antigen-presenting cells (APCs), which capture, process, and present antigens using major histocompatibility complex (MHC) molecules. This interaction ensures accurate identification of foreign substances. Activation of T-cells and B-cells also depends on surface markers, with T-cells requiring co-stimulatory signals from APCs and B-cells using surface immunoglobulins to recognize antigens. During the effector phase, cell surface markers guide immune cells to their targets, enabling cytotoxic T-cells to destroy infected cells and antibodies to mark pathogens for elimination by other immune cells. Regulatory T-cells (Tregs) express markers that suppress excessive immune responses, maintaining tolerance to self-antigens. Memory T-cells and B-cells, characterized by specific markers, persist after infection, enabling rapid responses to future exposures. Understanding these markers is crucial for developing therapies like monoclonal antibodies for cancer and autoimmune diseases, as well as designing vaccines that elicit strong immune responses. Thus, cell surface markers are indispensable for the immune response, facilitating antigen recognition, cell activation, targeting, and regulation. Markers like CD3 (view-product) are essential for the activation and regulation of T-cells, which are key players in the immune system.
  2. Cell Signaling: Cell surface markers are pivotal in cell signaling, facilitating communication between cells and triggering specific cellular responses. These markers, often proteins or glycoproteins, are located on the cell membrane and play crucial roles in transmitting signals from the extracellular environment to the cell's interior. In immune cells, surface markers like receptors and co-receptors bind to ligands or antigens, initiating a cascade of intracellular signaling events. This process is essential for the activation, differentiation, and function of immune cells. For example, when a T-cell receptor (TCR) on the surface of a T-cell binds to an antigen presented by an APC, it triggers a signaling pathway that results in T-cell activation and proliferation. Similarly, B-cell receptors (BCRs) on B-cells recognize specific antigens, leading to antibody production. Cell surface markers also regulate the intensity and duration of signaling, ensuring appropriate cellular responses. Dysregulation of these markers can lead to diseases such as cancer and autoimmunity. Understanding the role of cell surface markers in cell signaling is critical for developing targeted therapies and improving immunotherapies, as these markers provide specific targets for intervention. Thus, cell surface markers are indispensable for accurate and efficient cell signaling, which is fundamental to immune function and overall cellular communication. Proteins such as CD243 (Click-here) (P-glycoprotein) are involved in signaling pathways that regulate cellular functions like drug resistance in cancer cells.
  3. Cell Adhesion:  Cell adhesion, facilitated by cell surface markers, is essential for maintaining tissue structure, regulating immune responses, and orchestrating developmental processes. These markers, such as integrins and cadherins, mediate interactions between cells and with the extracellular matrix. Integrins bind to components of the extracellular matrix, providing anchorage and stability to cells within tissues. Cadherins facilitate calcium-dependent adhesion between adjacent cells, contributing to tissue integrity and organization during development. Additionally, cell adhesion molecules on immune cells enable them to adhere to endothelial cells and migrate to sites of infection, crucial for effective immune responses. The intricate roles of cell surface markers in cell adhesion underscore their significance in physiological processes and highlight their potential as therapeutic targets for various diseases affecting tissue integrity and immune function. Molecules like CD172g (SIRPγ) participate in cell-cell adhesion processes, which are important for maintaining tissue structure and immune responses.
  4. Disease Identification:  Cell surface markers are pivotal in disease identification, serving as distinctive identifiers on cell membranes that aid in the recognition and diagnosis of various medical conditions. These markers, composed of proteins and glycoproteins, provide crucial information about the identity and status of cells, making them indispensable in medical diagnostics. Diagnostic biomarkers derived from cell surface markers enable clinicians to pinpoint specific cell types associated with diseases such as cancer, autoimmune disorders, and infectious diseases. For example, aberrant expression of markers like HER2/neu in breast cancer cells or CD markers in hematologic malignancies can indicate disease presence and severity. Immunophenotyping techniques further leverage these markers to analyze and classify abnormal cell populations, aiding in precise diagnosis and treatment monitoring. Monitoring changes in marker expression over time provides insights into disease progression and therapeutic responses, guiding personalized treatment strategies. Overall, the role of cell surface markers in disease identification underscores their significance in clinical practice, offering valuable tools for early detection, prognosis, and management of diverse medical conditions. Certain markers, such as HLA-C, are used to identify and monitor disease states, including autoimmune conditions and cancer.