title: Molecular mimics can induce novel self peptide-reactive CD4+ T cell clonotypes in autoimmune disease.
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 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.
authors.affiliation: Department of Microbiology-Immunology, Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Ercolini
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D006192:Haemophilus Infections / Q000150:complications / Q000276:immunology; D006193:Haemophilus influenzae / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D010447:Peptide Hydrolases / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D009185:Myelin Proteins; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010447:Peptide Hydrolases; C030732:protease IV