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

Abstract

Abstract 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 PLP139–151, which is contained within the protease IV protein of Haemophilus influenzae (HAE574–586). We describe an IFN-γ-producing Vβ19+ T cell population in HAE574–586-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 PLP139–151, 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.