MHC restriction to T-cell autoaggression: an emerging understanding of IDDM pathogenesis

The Nobel prize-winning discovery of MHC restriction by Zinkernagel and Doherty has led to some of the most exciting advances in immunology over the past two decades. The ongoing progress in our conceptual understanding of the processes governing the immunology to infection, tolerance to self and consequently the immune dysregulation in autoimmunity have all assimilated the laws of restriction as a central tenet. The focus of much of this research has been the T-cell and its interactions. Refinement of the paradigm of MHC restriction at the molecular level has allowed a view of the pathogenesis of insulin-dependent diabetes mellitus (IDDM), a prototypic autoimmune disease, unprecedented in its detail. This article discusses the impact of MHC restriction on the central themes of immunology, and focuses on its utility as a framework in understanding the role of the T-cell in the pathogenesis of IDDM.