title: Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns.
abstract: Studies of repertoires of mouse monoclonal CD4(+) T cells have revealed several mechanisms of self-tolerance; however, which mechanisms operate in normal repertoires is unclear. Here we studied polyclonal CD4(+) T cells specific for green fluorescent protein expressed in various organs, which allowed us to determine the effects of specific expression patterns on the same epitope-specific T cells. Peptides presented uniformly by thymic antigen-presenting cells were tolerated by clonal deletion, whereas peptides excluded from the thymus were ignored. Peptides with limited thymic expression induced partial clonal deletion and impaired effector T cell potential but enhanced regulatory T cell potential. These mechanisms were also active for T cell populations specific for endogenously expressed self antigens. Thus, the immunotolerance of polyclonal CD4(+) T cells was maintained by distinct mechanisms, according to self-peptide expression patterns.
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Deepali
authors.identifier: http://orcid.org/0000-0002-8215-7639
authors.initials: D
authors.lastname: Malhotra
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Linehan
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Thamotharampillai
authors.initials: T
authors.lastname: Dileepan
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: You Jeong
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Diabetes Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Whitney E
authors.initials: WE
authors.lastname: Purtha
authors.affiliation: Diabetes Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Nelson
authors.affiliation: Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fife
authors.affiliation: Department of Laboratory Medicine and Pathology, Institute for Translational Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Harry T
authors.initials: HT
authors.lastname: Orr
authors.affiliation: Diabetes Center, University of California San Francisco, San Francisco, California, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Marc K
authors.identifier: http://orcid.org/0000-0001-8009-7655
authors.initials: MK
authors.lastname: Jenkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D010455:Peptides