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J Autoimmun. 2007 Dec;29(4):262-71. Epub 2007 Sep 17.

Death, adaptation and regulation: the three pillars of immune tolerance restrict the risk of autoimmune disease caused by molecular mimicry.

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University of Edinburgh, Institute of Immunology and Infection Research, School of Biological Sciences, Kings Buildings, West Mains Road, Edinburgh, EH9 3JT, UK.


Extensive cross-reactivity in T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes seems to be essential to give sufficient immune surveillance against invading pathogens. This carries with it an inherent risk that T cells activated during a response to clear an infection can, perhaps years later, respond to a self pMHC of sufficient similarity. This lies at the heart of the molecular mimicry theory. Here we discuss our studies on the disease-causing potential of altered peptide ligands (APL) based on the sequence of a single autoantigenic epitope, the Ac1-9 peptide of myelin basic protein that induces experimental autoimmune encephalomyelitis in mice. These show that the window of similarity to self for induction of disease by cross-reactive non-self peptides is actually quite restricted. We show that each of the three pillars of immune tolerance (death, anergy/adaptation and regulation) has a role in limiting the risk of molecular mimicry by maintaining a threshold for harm.

[Indexed for MEDLINE]

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