Springer Protocols: Abstract: Etiology of Autoimmmune Disease: How T Cells Escape Self-Tolerance

Etiology of Autoimmmune Disease: How T Cells Escape Self-Tolerance

By: Eli Sercarz², Claudia Raja-Gabaglia²

Abstract

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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 histocompatibility complex molecules. Another escape mechanism involves avoidance of the regulatory circuitry.

Affiliation(s): (2) Torrey Pines Institute for Molecular Studies, San Diego, CA

Book Title: Immunological Tolerance: Methods and Protocols

Series: Methods in Molecular Biology | Volume: 380 | Pub. Date: Jun-08-2007 | Page Range: 271-283 | DOI: 10.1007/978-1-59745-395-0_16

Subject: Immunology

Key Words: Intramolecular sequestration - antigen processing and presentation - T-cell repertoire - immune regulation - immunodominance - thymic antigen expression - crypticity - immune hierarchies

References

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