The immune system protects the body from invaders like bacteria and viruses, relying on a diverse army of cells. Among these, T cells play a central role in recognizing and eliminating threats. A molecule called CD45RA, found on the surface of these immune cells, is an important marker that helps distinguish different types of T cells and provides insights into their roles in the body’s defenses. Understanding CD45RA helps us learn more about how our immune system works and responds to various challenges.
What is CD45 and CD45RA?
CD45, also known as Leukocyte Common Antigen, is a large protein located on the surface of nearly all white blood cells. This protein functions as a protein tyrosine phosphatase (PTP), meaning it removes phosphate groups from other proteins. This activity is important for regulating cell signaling pathways, particularly those involved in activating immune cells.
CD45 exists in several different versions, called isoforms, which arise from alternative splicing. This process allows different combinations of gene segments to be included or excluded, leading to distinct protein structures. CD45RA is one such isoform, characterized by the presence of specific protein segments.
CD45RA expression is not uniform across all white blood cells; it is found on naive T cells. Naive T cells are immune cells that have not yet encountered a specific foreign substance (antigen). The distinct structure of CD45RA helps these cells maintain their naive state.
Role in Immune Cell Identification
The presence or absence of CD45RA is widely used to identify and categorize different T cell populations. Naive T cells, which have not encountered their specific antigen, express high levels of CD45RA. This expression distinguishes them from memory T cells, which have previously been activated by an antigen and express a different isoform, CD45RO.
By combining CD45RA with other surface markers, T cell identification can be further refined. For instance, naive T cells are identified by co-expression of CD45RA and CCR7 (CD45RA+ CCR7+). In contrast, TEMRA cells, a type of memory T cell, also express CD45RA but lack CCR7 (CD45RA+ CCR7-). This differential expression helps assess an individual’s immune status, reflecting the balance between newly generated and experienced immune cells.
How CD45RA Influences Immune Responses
CD45, as a phosphatase, influences the signaling cascades within T cells, especially those initiated by the T cell receptor (TCR). The specific CD45RA isoform, due to its larger extracellular domain, affects the activation threshold of naive T cells. This larger size can lead to different interactions with other molecules on the cell surface, such as the kinase Lck.
The larger CD45RA isoform reduces the efficiency of TCR signaling. This structural difference makes naive T cells less easily activated than memory T cells, which express the smaller CD45RO isoform. Naive T cells require a stronger, more sustained signal to activate and initiate an immune response. This ensures that only strong antigenic signals trigger new T cell activation, preventing unwanted or excessive immune reactions.
CD45RA in Health and Disease
Changes in the proportion of CD45RA-expressing T cells indicate immune health and disease progression. For example, in aging, a process known as immunosenescence occurs, where the number of naive T cells, and thus CD45RA+ T cells, decreases. This reflects a reduced capacity to respond to new infections or vaccinations.
CD45RA expression is relevant in various disease contexts. In chronic infections, autoimmune diseases, and acute conditions like sepsis, the balance between CD45RA- and CD45RO-expressing cells shifts significantly. These changes can serve as biomarkers, offering insights into disease progression, immune dysfunction, or predicting outcomes. In some cancers, the ratio of naive to memory T cells, identifiable by CD45RA and CD45RO expression, has been explored as a prognostic indicator.