title: T-cell "induced-self" MHC class I/peptide complexes may enable "de novo" tolerance induction to neo-antigens occurring outside of the thymus: Lessons from the hair follicle.
abstract: The hair follicle (HF) epithelium can present self-antigens to cognate CD8+ T cells. These cells express periodically during the hair cycle arising or age-related immunogenic proteins including HF-specific neo-antigens. We propose that IFN-gamma derived from the respective antigen-specific T cells spotting the particular self-peptides may thereby significantly induce and alter self-antigen presentation ("induced-self"). This induction, at first, may silence T cells, including neo-epitope-specific T cells. As the thymus cannot significantly recapitulate neo-epitopes evolving in the periphery, we propose that peripheral tissue-specific induction of MHC molecules presenting exactly these neo-epitopes by self-MHC/peptide-reactive CD8+ T cells is a key element of self-tolerance. Subsequently, however, the local perpetuation and modification of the same crosstalk in the context of HF immune privilege collapse can invite HF immunopathology, as typically seen in alopecia areata. This concept may essentially complement thymus-based regulation models of self/non-self-discrimination beyond "missing-self" to the fine-tuned "induced-self" to ensure peripheral needs to maintain self-tolerance in the case of "danger" and any "alteration of self".
authors.affiliation: Independent Research HD (IRHD), Heidelberg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Oelert
authors.affiliation: Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Gilhar
authors.affiliation: Centre for Dermatology Research, University of Manchester, Manchester, UK.|Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000506:Alopecia Areata / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D000939:Epitopes / Q000276:immunology; D018859:Hair Follicle / Q000473:pathology*; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D000941:Antigens; D001324:Autoantigens; D000939:Epitopes; D007371:Interferon-gamma
keywords: autoimmunity; cytotoxic T cells; immune regulation; immunity; neo-antigen