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

Abstract

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.

• Authors: Kelli R Ryan, Sarju D Patel, Leigh A Stephens, Stephen M Anderton
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 29 Issue 4 Pg. 262-71 (Dec 2007) ISSN: 0896-8411 [Print] England
• PMID: 17870412 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Autoantibodies
• Autoantigens
• Receptors, Antigen, T-Cell

Topics

• Adaptation, Physiological (immunology)
• Animals
• Autoantibodies (immunology)
• Autoantigens (immunology)
• Autoimmune Diseases
• Autoimmunity
• Cell Death
• Humans
• Immune Tolerance
• Infections (immunology)
• Molecular Mimicry
• Receptors, Antigen, T-Cell (immunology)
• T-Lymphocytes (immunology)