Autophagy in Autoimmunity

Macroautophagy, a homeostatic process that shuttles cytoplasmic constituents into endosomal and lysosomal compartments, delivers antigens for presentation on major histocompatibility complex (MHC) molecules. Autophagy-mediated antigen processing in thymic epithelial cells has been suggested to be involved in the generation of a self-MHC restricted and self-tolerant CD4⁺ T cell repertoire. Although autophagy was initially described to deliver intracellular antigens to MHC class II loading compartments, its molecular machinery has now also been described to enhance the delivery of extracellular antigens. This review describes the mechanisms by which the immune system utilizes autophagy to shape and regulate CD4⁺ T cell responses during tolerance induction and following immune activation.