T cell response to preproinsulin I and II in the nonobese diabetic mouse.
Immunization against insulin, insulin B chain, or B chain peptide B(9-23) (preproinsulin peptide II(33-47)) prevents diabetes in the nonobese diabetic (NOD) mouse. Whether or not peptide II(33-47) is the only proinsulin determinant recognized by CD4 T cells remains unclear. Using two peptide libraries spanning the entire sequence of preproinsulin I and preproinsulin II, respectively, we identified T cells specific for four proinsulin epitopes within the islet cell infiltrate of prediabetic female NOD mice. These epitopes were among immunogenic epitopes to which a T cell response was detected after immunization of NOD mice with individual peptides in CFA. Immunogenic epitopes were found on both isoforms of insulin, especially proinsulin II, which is the isoform expressed in the thymus. The autoimmune response to proinsulin represented only part of the immune response to islet cells within the islet cell infiltrate in 15-wk-old NOD mice. This is the first systematic study of preproinsulin T cell epitopes in the NOD mouse model.
Institut National de la Santé et de la Recherche Médicale Unité 561, Hôpital Cochin-Saint Vincent de Paul, Paris, France.
Philippe
P
Halbout
Jean-Paul
JP
Briand
Chantal
C
Bécourt
Sylviane
S
Muller
Christian
C
Boitard
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007279:Injections, Subcutaneous; D007328:Insulin; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011236:Prediabetic State / Q000276:immunology; D011384:Proinsulin / Q000008:administration & dosage / Q000276:immunology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D016693:Receptors, Antigen, T-Cell, alpha-beta; C013737:preproinsulin; D011384:Proinsulin