autoantigener

An autoantigen is a self molecule, typically a protein, nucleic acid, or lipid, that can be recognized by the adaptive immune system. In healthy individuals, central and peripheral tolerance limit or eliminate self-reactive lymphocytes to prevent autoimmunity. When tolerance fails or self-antigens are altered, released, or presented in inflammatory contexts, autoantigens may trigger autoimmune responses.

Autoantigens can be tissue-specific, such as myelin basic protein in the nervous system, or ubiquitous, like DNA, histones, or ribonucleoproteins. They may arise from post-translational modifications (for example citrullination or oxidation) or protein misfolding, which can create neoepitopes that are more immunogenic than the native form. Autoantibodies against autoantigens are common clinical markers and assist in diagnosing autoimmune diseases.

Common examples include anti-dsDNA and anti-nucleosome antibodies in systemic lupus erythematosus, anti-Ro/SSA and anti-La/SSB in Sjögren’s syndrome, thyroid peroxidase antibodies in autoimmune thyroiditis, anti-GAD65 or insulin in type 1 diabetes, and anti-citrullinated peptide antibodies in rheumatoid arthritis. T-cell–mediated responses to autoantigens can also contribute to tissue injury in various disorders.

Exposure to autoantigens can occur through cell death, defective clearance of apoptotic debris, or molecular mimicry with environmental agents. Epitope spreading may broaden autoreactivity over time. While most clinical focus is on autoantibody measurement for diagnosis, understanding autoantigens informs research into tolerance-inducing therapies and antigen-specific immunomodulation.