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Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2550-5. doi: 10.1073/pnas.0914508107. Epub 2010 Jan 20.

Molecular mimics can induce a nonautoaggressive repertoire that preempts induction of autoimmunity.

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La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.


To determine the role that competition plays in a molecular mimic's capacity to induce autoimmunity, we studied the ability of naïve encephalitogenic T cells to expand in response to agonist altered peptide ligands (APLs), some capable of stimulating both self-directed and exclusively APL-specific T cells. Our results show that although the APLs capable of stimulating exclusively APL-specific T cells are able to expand encephalitogenic T cells in vitro, the encephalitogenic repertoire is effectively outcompeted in vivo when the APL is used as the priming immunogen. Competition as a mechanism was supported by: (i) the demonstration of a population of exclusively APL-specific T cells, (ii) an experiment in which an encephalitogenic T cell population was successfully outcompeted by adoptively transferred naïve T cells, and (iii) demonstrating that the elimination of competing T cells bestowed an APL with the ability to expand naïve encephalitogenic T cells in vivo. In total, these experiments support the existence of a reasonably broad T cell repertoire responsive to a molecular mimic (e.g., a microbial agent), of which the exclusively mimic-specific component tends to focus the immune response on the invading pathogen, whereas the rare cross-reactive, potentially autoreactive T cells are often preempted from becoming involved.

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