Receptor-type tyrosine-protein phosphatase C (CD45RA)

Receptor-type tyrosine-protein phosphatase C (PTPRC), widely known as CD45, is a critical type I transmembrane glycoprotein expressed on all nucleated hematopoietic cells [1, 2]. The CD45RA isoform is a high-molecular-weight variant produced by the alternative splicing of exon A, primarily localized on the surface of naive T cells, as well as specific subsets of B cells and NK cells [1, 3, 8]. Biologically, CD45RA serves as an essential regulator of immune cell activation by dephosphorylating Src-family kinases like Lck and Fyn, which are required for T-cell and B-cell antigen receptor signaling [2, 12]. In clinical medicine, CD45RA is a significant marker for identifying leukemia stem cells in acute myeloid leukemia (AML) and is a primary target for selective depletion of naive T cells to prevent graft-versus-host disease (GVHD) in stem cell transplantation [14, 16]. Therapeutic strategies include radioimmunotherapy (e.g., Iomab-B) and experimental antibody-drug conjugates like Hm3A4-Ranpirnase designed to eliminate malignant clones [3, 14]. Furthermore, the expression of CD45RA is utilized as a biomarker to predict patient responses to immune checkpoint inhibitors and to monitor the maturation state of the immune system [9, 10, 17]. Due to its broad expression across the hematopoietic lineage, therapeutic targeting requires high specificity to avoid severe myelosuppression and generalized immunodeficiency [5, 14].

Other names

PTPRCCD45Leukocyte common antigenLCAT200GP180Ly-5B220

CD45RA acts as a protein tyrosine phosphatase that dephosphorylates the inhibitory C-terminal tyrosine of Src-family kinases (such as Lck and Fyn), thereby facilitating the initiation of T-cell and B-cell receptor signaling [1, 8, 12]. Therapeutic agents targeting CD45RA typically utilize monoclonal antibodies or antibody-drug conjugates to induce targeted cell depletion via antibody-dependent cellular cytotoxicity (ADCC) or the delivery of cytotoxic payloads to malignant or autoreactive cells [11, 14].