title: Exploring the MHC-peptide matrix of central tolerance in the human thymus.
abstract: Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant cross-talk between major histocompatibility complex-class I and II pathways and differences in source protein representation between individuals as well as different antigen-presenting cells. Furthermore, several autoimmune- and tumour-related peptides, from enolase and vimentin for example, are presented in the healthy thymus. 302 peptides are directly derived from negatively selecting dendritic cells, thus providing the first global view of the peptide matrix in the human thymus that imposes self-tolerance in vivo.
authors.affiliation: Department of General Neurology, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
authors.forename: Eleni
authors.initials: E
authors.lastname: Adamopoulou
authors.forename: Stefan
authors.initials: S
authors.lastname: Tenzer
authors.forename: Nina
authors.initials: N
authors.lastname: Hillen
authors.forename: Paula
authors.initials: P
authors.lastname: Klug
authors.forename: Ioanna A
authors.initials: IA
authors.lastname: Rota
authors.forename: Silvia
authors.initials: S
authors.lastname: Tietz
authors.forename: Madlen
authors.initials: M
authors.lastname: Gebhardt
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Eva
authors.initials: E
authors.lastname: Tolosa
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Christina
authors.initials: C
authors.lastname: Stoeckle
mesh_terms: D000293:Adolescent; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D061167:Central Tolerance / Q000276:immunology*; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007223:Infant; D008024:Ligands; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D022423:Myeloid Cells / Q000166:cytology; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D001324:Autoantigens; D039521:CD11c Antigen; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010455:Peptides