Generation of T-Cell Antigenic Determinants in Autoimmunity and Their Recognition

This chapter discusses the cellular strategy inherent in the creation of the self-determinants that become involved in autoreactivity. There is no common structural characteristic describing antigenic determinants involved in autoimmunity. T lymphocytes directed against such determinants have managed to escape negative selection, and their emergence into pathogenicity is contextual. The "dominant self" that does induce negative selection is created by the ordeal of antigen-processing events. The residual self-reactive potential, inherent in the "cryptic self," may erupt into autoimmune attack when fortuitously cross-reactive, dominant determinants are encountered, or upon interaction with environmental agents that excite Toll-like receptors, or provide unusual cell-activation stimuli. Deficiencies in regulation at a variety of points can alternatively unleash the available repertoire, largely directed against the cryptic self. To conclude, autoimmune disease is an outcome dependent on a string of chance events, some genetically underwritten and others related to a series of immunologic events in the lifetime of the individual that prey upon the residual self-reactive repertoire.