Naturally processed heterodimeric disulfide-linked insulin peptides bind to major histocompatibility class II molecules on thymic epithelial cells.
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.
Forquet
F
F
Banting and Best Department of Medical Research, University of Toronto, ON, Canada.
Hadzija
M
M
Semple
J W
JW
Speck
E
E
Delovitch
T L
TL
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*
D004220:Disulfides; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D010455:Peptides; D011994:Recombinant Proteins