On the surface of the body’s immune cells is a protein called CD45, also known as the Leukocyte Common Antigen (LCA). This molecule is found on all nucleated hematopoietic cells, including the white blood cells responsible for fighting infection. The protein’s presence on these cells allows for the identification and regulation of immune responses.
The Structure and Variants of CD45
CD45 is a transmembrane protein, meaning part of it sits outside the cell, a section passes through the cell’s outer membrane, and another part resides inside the cell. The portion inside the cell is a protein tyrosine phosphatase (PTP), which removes phosphate groups from other proteins as a form of cellular communication. The structure of this internal part is highly conserved across species and features two PTP domains, though only one is enzymatically active.
The external part of the CD45 protein is where variation occurs. Through a process called alternative splicing, different sections of the CD45 gene can be included or excluded from the final protein. This results in several different versions, or isoforms, of CD45. These isoforms are distinguished by their size and are expressed on different types of immune cells depending on their activation and differentiation state.
Two of the most well-known variants are CD45RA and CD45RO. CD45RA is a large isoform found on naive T-cells—immune cells that have not yet encountered a foreign substance, or antigen. In contrast, CD45RO is the shortest isoform and is characteristic of memory T-cells, which have been previously activated by an antigen and are prepared for a faster response in the future. This difference is like giving soldiers distinct uniforms based on their experience: naive T-cells wear the CD45RA version, while seasoned memory T-cells wear the CD45RO version.
The Core Function of CD45 in Immune Cells
The primary role of CD45 is to regulate signaling pathways within immune cells. Inside the cell, CD45 removes inhibitory phosphate groups from proteins called Src family kinases (SFKs), such as Lck and Fyn in T-cells. This dephosphorylation event activates these kinases, which in turn initiates a cascade of signals that tells the cell to respond.
This regulatory action is like a master switch for the immune response. For a T-cell or B-cell to become fully activated, CD45 must function correctly to permit internal signaling. Without this initial action, the signal from the antigen receptor is stalled, and the cell fails to mount an effective response, as confirmed by studies on cells lacking CD45.
The balance of CD45’s activity is delicate. If it is not functioning, immune cells cannot be properly activated, potentially leading to immunodeficiency. Conversely, if its regulatory role is disrupted, it could contribute to an overactive immune response, which is a factor in autoimmune diseases. By controlling the activation threshold of lymphocytes, CD45 ensures that immune cells respond appropriately to external stimuli.
CD45 as a Cellular Identity Marker
In scientific research and clinical laboratories, proteins on a cell’s surface are used as “markers” to distinguish cell types. Because CD45 is expressed by nearly all leukocytes but not by other cells like mature red blood cells or platelets, it serves as a primary pan-leukocyte marker. This allows scientists to identify and isolate the entire family of white blood cells.
This characteristic is utilized in a technique called flow cytometry, which uses lasers to analyze millions of cells in a fluid sample like blood. Cells are first tagged with antibodies specific to certain markers and linked to fluorescent dyes. As the cells pass one-by-one through the laser beam, the dyes light up, allowing a machine to count and sort them based on the markers they carry.
In this process, CD45 is often the first marker used to isolate the entire population of immune cells from other components in the sample. This initial step is frequently referred to as “CD45 gating.” Once the leukocyte population has been identified using this gate, scientists can then use other, more specific markers to further subdivide the population into distinct groups like T-cells, B-cells, and monocytes.
Role in Diagnosing and Monitoring Disease
The function of CD45 as an identifier extends into clinical medicine, where it is used to diagnose and classify blood cancers like leukemia and lymphoma. The expression level of CD45 on cancerous cells can differ from that of healthy immune cells. For instance, certain types of acute lymphoblastic leukemia (ALL) are characterized by immature cancer cells that show dim or negative CD45 expression.
Using flow cytometry, clinicians analyze the intensity of the CD45 signal on a patient’s cells to identify aberrant populations. For example, in diagnosing B-cell chronic lymphocytic leukemia (CLL), the cancerous cells show lower CD45 density compared to normal lymphocytes. This “CD45 dim” signature, combined with other cell markers, contributes to a precise diagnosis and classification of the disorder.
Beyond initial diagnosis, CD45 is also important for monitoring patients after medical procedures such as bone marrow transplantation. Following a transplant, clinicians track the regeneration of the patient’s immune system by monitoring the presence of donor-derived CD45-positive cells. The selective depletion of certain CD45-expressing cells from donor grafts is a strategy being explored to reduce complications like graft-versus-host disease (GvHD).