CD247

CD247 Full Name

CD247 molecule

CD247 Introduction

CD247, also known as the T-cell surface glycoprotein CD3 zeta chain or CD3ζ, is a critical signaling subunit of the T-cell receptor (TCR)–CD3 complex that is encoded by the CD247 gene on human chromosome 1. It consists of a transmembrane protein containing multiple immunoreceptor tyrosine-based activation motifs (ITAMs) in its intracellular domain, which become phosphorylated upon antigen recognition. These ITAMs provide docking sites for downstream signaling molecules such as ZAP-70, linking antigen binding by the TCR to intracellular signal transduction pathways that drive T-cell activation, proliferation and effector differentiation. CD247's role within the TCR–CD3 complex is indispensable for effective adaptive immune responses, and its expression level directly influences T-cell signal strength and functional competence.

Figure 1. T-cell receptor (TCR) complex composed of α and β chains for antigen recognition, associated noncoavalently with CD3γε and CD3δε heterodimers, and a CD3ζ (CD247) homodimer.(Sources: Macpherson AM, et al.; 2020)

Functionally, CD247's primary role is transducing activation signals in T cells and other lymphocytes, including some natural killer (NK) cell subsets, upon engagement of antigen-presenting major histocompatibility complex (MHC) molecules. Through phosphorylation of its ITAMs by Src family kinases such as LCK and FYN, CD247 recruits and activates ZAP-70, which then propagates downstream signaling cascades including MAP kinase and NF-κB pathways that coordinate gene expression for immune responses. Because of its central role in TCR signaling, CD247 expression and function are often studied using specific antibodies, flow cytometry panels, ELISA kits and detection reagents in immunological research to monitor T-cell activation status, immune synapse formation, and adaptive immunity.

In disease contexts, alterations in CD247 expression or structure are associated with immune dysregulation and clinical pathology. Genetic defects affecting CD247 can contribute to immunodeficiency phenotypes, such as T-B+ severe combined immunodeficiency, where impaired signaling through the TCR leads to defective adaptive immunity. Polymorphisms and reduced CD247 expression have been linked to autoimmune disorders including systemic lupus erythematosus and juvenile idiopathic arthritis, suggesting an impact on immune tolerance and activation thresholds. Beyond autoimmunity, downregulated CD247 has emerged as a potential biomarker for disease severity and prognosis in chronic inflammatory conditions such as idiopathic pulmonary fibrosis and type 2 diabetes, where lower expression correlates with poorer outcomes and altered immune cell activity. In oncology, CD247 expression may influence tumor immune surveillance and has been investigated as a prognostic indicator in cancers such as head and neck squamous carcinoma, reflecting its broader relevance as both a biomarker and a therapeutic target in immunomodulatory research.

Alternate Names for CD247

CD247; CD247 molecule; T3Z; CD3H; CD3Q; CD3Z; TCRZ; IMD25; CD3-ZETA; T-cell surface glycoprotein CD3 zeta chain

• 1. Macpherson AM, et al.; Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy. J Clin Med. 2020, 9(9):2967.