title: During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities.
abstract: In the NOD mouse model of type 1 diabetes, major histocompatibilitycomplex (MHC) class I-restricted CD8(+) T cells are essential for disease development. However, the extent of diversity of their antigenic specificities during early pathogenesis remains unclear. An insulin-derived peptide was recently identified as the epitope for the NOD-derived diabetogenic T-cell clone G9C8. To explore the possibility that the early pathogenic CD8(+) T-cell population comprises additional antigenic specificities, we employed the T-cell clones AI4 and NY8.3, both of which are pathogenic and represent specificities present in early insulitic lesions. The clones responded to distinct fractions of chromatographically separated class I MHC-bound peptides purified from NOD-derived NIT-1 beta cells, and neither clone recognized the insulin-derived peptide. NIT-1 cells represent an unlimited peptide source that will allow for the future isolation and sequencing of the novel multiple epitopes targeted early in the autoimmune response by pathogenic CD8(+) T cells.
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. dilorenz@aecom.yu.edu
authors.forename: Teresa P
authors.initials: TP
authors.lastname: DiLorenzo
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lieberman
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takaki
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Honda
authors.forename: Harold D
authors.initials: HD
authors.lastname: Chapman
authors.forename: Pere
authors.initials: P
authors.lastname: Santamaria
authors.forename: David V
authors.initials: DV
authors.lastname: Serreze
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Nathenson
mesh_terms: D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011236:Prediabetic State / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007328:Insulin