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Molecular Mimics Can Induce Novel Self Peptide-Reactive CD4⁺ T Cell Clonotypes in Autoimmune Disease¹

Department of Microbiology-Immunology, Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611

It has been postulated that infectious agents may precipitate autoimmune disease when T cell responses raised against the pathogen cross-react with self-peptides, a phenomenon known as molecular mimicry. However, there are very little data available characterizing the similarity between the repertoire of the cross-reactive self-specific T cell population compared with the pathogen-specific T cell repertoire. In this study, we use immunoscope analysis to identify the T cell populations induced upon priming SJL/J mice with a pathogen-derived mimic of the immunodominant encephalitogenic myelin peptide PLP_139–151, which is contained within the protease IV protein of Haemophilus influenzae (HAE_574–586). We describe an IFN--producing Vβ19⁺ T cell population in HAE_574–586-primed mice that appears to be the "public clonotype" as it expanded in response to peptide in all mice tested. Critically this Vβ19⁺ T cell population is not expanded in mice primed with the self-peptide PLP_139–151, indicating that mimics can induce the expansion of new self-reactive populations not initially present in the periphery of a host. This is the first description of the use of immunoscope analysis to characterize the cross-reactive anti-self T cell response induced by a molecular mimic.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by United States Public Health Service, National Institutes of Health Grants NS-040460 and NS-023349, and National Multiple Sclerosis Society (NMSS) Research Grant RG-3166-A-4. A.M.E. was supported by National Multiple Sclerosis Society (NMSS) Postdoctoral Fellowship Grant FG-1596-A-1.

² Address correspondence and reprint requests to Dr. Stephen D. Miller, Northwestern University Medical School, 303 East Chicago Avenue, Chicago IL. E-mail address: s-d-miller{at}northwestern.edu

³ Abbreviations used in this paper: MS, Multiple Sclerosis; TMEV, Theiler’s murine encephalomyelitis virus.