Endoplasmic Reticulum Aminopeptidase 2, or ERAP2, is a protein within the immune system. It plays a role in the body’s defense mechanisms, helping it identify and respond to various threats. Understanding ERAP2 offers insights into the processes that maintain overall health.
Understanding ERAP2’s Function
ERAP2 operates as an enzyme, a protein that speeds up chemical reactions within cells. Its function involves trimming peptides inside the endoplasmic reticulum, a network of membranes within the cell. This process adjusts the length of peptides, which are small chains of amino acids. Accurate sizing is necessary for their proper loading onto Major Histocompatibility Complex (MHC) class I molecules.
MHC class I molecules are cell surface proteins that display these trimmed peptides. Once loaded, these peptide-MHC complexes are transported to the cell surface. There, they are presented to T cells, a type of white blood cell that surveys the body for abnormalities. This presentation allows the immune system to recognize and signal for elimination cells that are infected with viruses or have become cancerous.
How ERAP2 Influences Immune Responses
The specific peptides ERAP2 processes directly influence the peptides presented by MHC class I molecules. By trimming peptides, ERAP2 helps determine which protein fragments from within a cell are displayed on its surface. This selection affects the activation and specificity of cytotoxic T lymphocytes (CTLs), specialized immune cells that detect and destroy infected or abnormal cells.
ERAP2 activity ensures that a diverse set of peptides is presented, allowing CTLs to effectively recognize and target threats. This contributes to immune surveillance, the body’s monitoring for signs of disease. The immune system’s ability to distinguish between “self” (healthy body cells) and “non-self” (pathogens or cancerous cells) relies on the accurate presentation of these peptide fragments. Without proper peptide trimming by enzymes like ERAP2, the immune response might be less effective or even misdirected.
Genetic Differences and ERAP2 Activity
Individuals can exhibit variations in their ERAP2 gene, which codes for the ERAP2 protein. These genetic differences, known as polymorphisms, mean that people may produce ERAP2 proteins with varying levels of activity or even non-functional versions. One well-studied polymorphism, rs2248374, can lead to either a fully functional ERAP2 protein or a significantly less active form. This variation influences how the gene is translated into a protein.
The presence of a non-functional or less active ERAP2 protein alters the peptide trimming process within cells. Consequently, the repertoire of peptides presented by MHC class I molecules can change. These genetic differences contribute to the wide range of individual immune responses. Such variations can also influence a person’s susceptibility to certain health conditions.
ERAP2’s Connection to Health Conditions
Variations in the ERAP2 gene and its protein activity have been linked to several health conditions. In autoimmune diseases, where the immune system mistakenly attacks healthy body tissues, altered ERAP2 function may play a role. For example, ERAP2 variants have been associated with an increased risk for conditions such as Behcet’s disease, psoriasis, ankylosing spondylitis, and Crohn’s disease. The proposed mechanism involves the presentation of “self” peptides that, due to improper trimming, trigger an autoimmune response.
Beyond autoimmune disorders, ERAP2’s influence extends to infectious diseases and certain cancers. Changes in ERAP2 activity can affect the immune system’s ability to effectively present pathogen-derived peptides, potentially impacting infection clearance. Similarly, in cancer, altered ERAP2 function might influence the presentation of tumor-specific peptides, affecting the immune system’s capacity to recognize and eliminate cancerous cells. This highlights the complex interplay between genetic factors and immune system regulation in disease development.