title: Naturally processed heterodimeric disulfide-linked insulin peptides bind to major histocompatibility class II molecules on thymic epithelial cells.
abstract: We determined whether disulfide-linked insulin peptides that are immunogenic in vitro for CD4+ T cells bind to major histocompatibility complex class II in vivo. Radiolabeled recombinant human insulin (rHI) was injected into BALB/c mice, and processed rHI peptides bound to I-Ad molecules on different thymic antigen-presenting cells were characterized. The A6-A11/B7-B19 and A19-A21/B14-B21 disulfide-linked I-Ad-bound rHI peptides were isolated from thymic epithelial cells but not dendritic cells. While both thymic epithelial cells and dendritic cells present rHI to HI/I-Ad-specific T cells, these antigen-presenting cells do not present the reduced or nonreduced forms of the disulfide-linked rHI peptides. Thus, a naturally processed disulfide-linked peptide can bind to major histocompatibility complex class II in vivo. The potential role of these peptides in immunological tolerance is discussed.
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, ON, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Forquet
authors.forename: M
authors.initials: M
authors.lastname: Hadzija
authors.forename: J W
authors.initials: JW
authors.lastname: Semple
authors.forename: E
authors.initials: E
authors.lastname: Speck
authors.forename: T L
authors.initials: TL
authors.lastname: Delovitch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D004220:Disulfides; D004848:Epithelium / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011485:Protein Binding; D011994:Recombinant Proteins; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D004220:Disulfides; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D010455:Peptides; D011994:Recombinant Proteins