Etiology of autoimmune disease: how T cells escape self-tolerance.
Despite central and peripheral regulatory mechanisms designed to prevent self-reactivity, autoimmune disease is a common condition. This article explores several ways in which both high and low affinity T cells can avoid negative selection. The concept of intramolecular sequestration indicates that there will be a hierarchy of presentation of different antigenic determinants derived from a protein antigen, such that some determinants will be efficiently presented whereas others will be poorly presented or not presented at all. Generally, only well-presented determinants will induce tolerance among T cells with sufficient affinity/avidity. Escape from this negative regulation can occur via effects of the antigen processing and presentation system denying determinants access to the peptide-binding grooves of major histo-compatibility complex molecules. Another escape mechanism involves avoidance of the regulatory circuitry.
Sercarz
Eli
E
Torrey Pines Institute for molecular Studies, San Diego, CA, USA.
Raja-Gabaglia
Claudia
C
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*