selfpeptides

Selfpeptides are peptide fragments derived from an organism’s own proteins that are generated inside cells and presented on the cell surface by major histocompatibility complex (MHC) molecules. They are continuously produced by intracellular proteolysis and serve as signals of cellular health to T cells. Distinct pathways generate peptides for MHC class I and class II antigen presentation.

In most cells, proteasomes degrade cytosolic proteins into short peptides, which are loaded onto MHC class I and displayed to CD8+ T cells. For MHC class II, peptides originate from endocytosed or autophagically processed proteins and are presented to CD4+ T cells in endosomal compartments.

Selfpeptides are central to immune tolerance. During T cell development in the thymus, T cells reactive to selfpeptides are deleted or edited, establishing tolerance to host proteins. Peripheral tolerance mechanisms further limit autoreactivity in mature individuals.

Failures in selfpeptide tolerance can contribute to autoimmunity, where autoreactive T or B cells attack host tissues. In cancer, tumor cells may present selfpeptides or altered self-peptides; such peptides can be targeted by immunotherapies or used as vaccine components, reflecting the dual role of selfpeptides in health and disease.

Researchers identify selfpeptides using mass spectrometry of MHC-bound peptides and study their role in tolerance and autoimmunity. Knowledge of selfpeptides informs vaccine design, autoimmunity therapies, and understanding of how the immune system distinguishes self from non-self.