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 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.

TNFR2 Deficiency Acts in Concert with Gut Microbiota To Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease

“…Exposure to different gut microbiota products, including short-chain fatty acid and polysaccharide A, may differentiate MOG-reactive CD4 + T cells into an autoreactive phenotype through molecular mimicry (89). It is also plausible that the induction of autoimmunity in the TNFR2 2/2 2D2 mice relies on a direct effect of gut microbiota on B cell function.…”

Bispecificity for Myelin and Neuronal Self-Antigens Is a Common Feature of CD4 T Cells in C57BL/6 Mice

“…One of the facets of polyspecificity in the context of autoimmune diseases is molecular mimicry, defined as sequence similarities between foreign and self-antigens that result in the cross-activation of autoreactive T and B cells by microbial Ags (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Originally, an important degree of sequence homology was considered necessary to explain molecular mimicry, but subsequent extensive dissection with synthetic peptide combinatorial libraries revealed that TCR Ag recognition is quite degenerate, and Ag similarity, resulting in the productive triggering of a given TCR, goes beyond sequence homology (10,38,39).…”

Comprendre le dialogue: l’interaction entre les micro-organismes et l’hôte

“…Une fois le processus activé, la réponse auto-immunitaire devient indépendante d'une exposition continue au facteur dé-clenchant environnemental et, de ce fait, le processus se perpétue de lui-même et est irréversible. Une réactivité croisée spécifique d'épitopes entre des micro-organismes et des tissus du soi a été démontrée dans certains modèles animaux [59] . Réciproquement, dans la plupart des maladies auto-immunes humaines, l'imitation moléculaire semble être un facteur de la progression d'une réponse auto-immune infraclinique préexistante et non un facteur de l'initiation d'une auto-immunité par rupture de la tolérance [60] .…”