The cluster of differentiation (CD) system, also referred to as classification determinant or cluster of designation, is a protocol for identifying and studying cell surface molecules, which serve as key targets for immunophenotyping. Physiologically, CD molecules often function as receptors or ligands crucial for cellular processes, initiating signal cascades that modify cell behavior. However, not all CD proteins are involved in signaling; some are essential for functions like cell adhesion.
Fig.1 Schematic diagram of CD.1
CD antigens, present in various immune cell populations, are key markers for identifying cell types and maturation stages. Notable examples include CD4 and CD8 on T cells, indicating helper and cytotoxic T cells, respectively. Techniques like flow cytometry and immunohistochemistry use CD markers to identify specific cells in immune responses, aiding in disease diagnosis, treatment development, and research. Key CD antigens encompass hematopoietic stem cell CD34 marker and leukocyte CD11/CD18 integrins. These antigens are crucial for cell activation, adhesion, and immune response regulation, and are widely used in cancer stem cell, and immunology research.
The CD nomenclature system was first established in 1982 at the 1st Human Leukocyte Differentiation Antigen (HLDA) Workshop in Paris, to classify the diverse monoclonal antibodies (mAbs) developed globally. If two distinct mAbs are verified to bind to one surface molecule, it is assigned a CD number. To date, over 300 unique CD clusters and subclusters have been identified. Initially used to clarify recognized molecules, CD designations, such as CD3 for a T cell surface protein, have enhanced communication in the field. CD molecule presence or absence in cell populations is denoted using '+' or '−' symbols, with variations like high, medium, or low indicating expression levels. Monitoring CD antigen expression profiles aids in identifying, isolating, and immunophenotyping cells in various immune processes.
Immunophenotyping and CD Marker Analysis
CD antigens serve as critical cell markers in immunophenotyping, facilitating the identification and isolation of specific leukocyte populations and lymphocyte subsets. Techniques like flow cytometry and immunohistochemistry (IHC) are employed to detect and quantify these markers on cell surfaces. The CD nomenclature system standardizes the designation of mAbs and the cell surface molecules they recognize, including receptors, adhesion molecules, enzymes, and glycans. This system is essential for diagnosing, classifying, and monitoring hematological malignancies, immunodeficiencies, and autoimmune diseases. In recent developments, mAbs directed against CD molecules have emerged as indispensable tools in the treatment of cancer and autoimmune conditions.
Fig.2 Expression map of CD1–CD100 across 42 distinct cell subsets.2, 3
CD Marker Expression in Solid Tumors
Leukocytes serve not only in defining immune responses but also prove instrumental in tumor detection. Therapeutically, antibodies targeting CD antigens are crucial for treating tumors and autoimmune diseases, and preventing organ transplant rejection. Additionally, assessing the ectopic expression of these markers in solid tumors has enhanced early disease detection. Epigenetic alterations in tumor cells result in increased aggressiveness and resistance to therapies by altering CD marker expression. Hypomethylation of CpG islands in CD marker gene promoters amplifies their expression on tumors, promoting tumor survival.
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