Molecular mimics can induce novel self peptide-reactive CD4+ T cell clonotypes in autoimmune disease

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-gamma-producing Vbeta19(+) 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 Vbeta19(+) 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.