The mechanisms by which host proteins with diverse expression patterns, sub-cellular localizations, and functions become targets of the immune response in autoimmune diseases remain unclear. The processing and presentation of autoantigenic epitopes relies on factors specific to the autoantigen itself, those present in the disease microenvironment, and the processing machinery of the individual. Many autoantigens across the spectrum of autoimmune diseases are united by their propensity to be modified. Although changes of the structure of proteins can be part of a normal homoeostatic process, aberrant proteolysis, post-translational modifications, mutations, or binding to foreign molecules, like medications, may alter normal antigen processing and presentation, leading to exposure of previously hidden epitopes.
It has also been observed that the tissues targeted in autoimmune diseases may express unique forms or increased levels of seemingly ubiquitously expressed autoantigens, or antigens of similar structure with those of infectious agents (molecular mimicry). At the same time, parameters intrinsic to the antigen presenting cells (both professional and non-professional), like specific HLA risk alleles, quantity of presenting HLA molecules, or factors that can affect the function and/or expression of antigen-processing machinery, like an infection or medications, can be crucial in interactions with autoantigenic T cells, thus leading to initiation and propagation of an autoimmune response. Finally, dysregulation of T cell regulatory mechanisms such as thymic selection, proliferative and inhibitory signaling is detrimental to the establishment of disease. Understanding the process leading to presentation of hidden autoantigenic epitopes and activation of autoantigenic T cells is critical in advancing our knowledge of autoimmunity, with implications to other fields, and can lead to development of targeted immunotherapies.
The Research Topic “Autoantigen Processing and Presentation” welcomes all topics covering factors affecting antigen processing, presentation, and recognition in autoimmunity. We welcome all types of manuscripts, including Case Reports, Original Research, Review and Mini Reviews. Articles can be focused on, but not limited to:
• Antigen modifications that alter antigen processing and presentation
• Inherent and acquired characteristics of antigen processing machinery
• Infectious or antitumor immune responses leading to autoimmunity through molecular mimicry or antigen modification
• Characterization of autoantigenic T cells
• Therapeutic implications of antigen-specific strategies
Dr. Naoto Hirano is a co-founder and shareholder of TCRyption/Treadwell Therapeutics, related to the development of T cell gene therapy. and holds patents in the field of T cell gene therapy. The other Topic Editors declare no competing interests in relation to this Research Topic.