Do the peptide-binding properties of diabetogenic class II molecules explain autoreactivity?
One seminal aspect in autoimmune diabetes is antigen presentation of beta cell antigens by the diabetes-propensity class II histocompatibility molecules. The binding properties of I-Ag7 molecules are reviewed here and an emphasis is placed on their selection of peptides with a highly specific sequence motif, in which one or more acidic amino acids are found at the carboxy end interacting at the P9 anchoring site of I-Ag7. The reasons for the central role of I-Ag7 in the autoimmune response are analyzed. The insulin B chain segment 9-23 is a hot spot for T cell selection and a striking example of a weak MHC binding peptide that triggers autoreactivity.
Suri
Anish
A
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Levisetti
Matteo G
MG
Unanue
Emil R
ER
D000818:Animals; D017951:Antigen Presentation; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D007328:Insulin; D010455:Peptides