Selfproteins

Selfproteins are proteins encoded by an organism’s own genome and expressed in its tissues under normal physiological conditions. They include enzymes, structural proteins, signaling molecules, and receptors that perform everyday cellular tasks and help define the body’s internal milieu. In immunology, selfproteins act as markers of “self” that the immune system is trained to tolerate.

The immune system distinguishes self from non-self through a combination of central and peripheral tolerance. Central tolerance eliminates many self-reactive lymphocytes during development in the thymus and bone marrow. Peripheral tolerance maintains non-responsiveness to self proteins in mature lymphocytes through mechanisms such as anergy, regulation by T cells, and deletion. When tolerance fails or self proteins are modified, self-proteins can become autoantigens, provoking autoreactive T or B cell responses and contributing to autoimmune disease. Self-protein fragments presented by major histocompatibility complex (MHC) molecules are central to these processes.

Examples of self-proteins include housekeeping enzymes, cytoskeletal components, and circulating proteins such as insulin, albumin, and various nuclear or cytoplasmic antigens. In autoimmune diseases, self-proteins like myelin basic protein, insulin, citrullinated peptides, and nuclear antigens (for example, Ro/SSA, dsDNA) can be targeted by autoantibodies or T cells, reflecting a breakdown of tolerance.

Research and clinical relevance centers on identifying self-proteins involved in autoimmunity, understanding how post-translational modifications create neoepitopes, and developing diagnostics, tolerance-inducing therapies, and personalized approaches to reduce inappropriate immune responses.