During the early prediabetic period in NOD mice, the pathogenic CD8+ T-cell population comprises multiple antigenic specificities

Teresa P. DiLorenzo, Scott M. Lieberman, Toshiyuki Takaki, Shinichiro Honda, Harold D. Chapman, Pere Santamaria, David V. Serreze, Stanley G. Nathenson

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

In the NOD mouse model of type 1 diabetes, major histocompatibility complex (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 β 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.

Original languageEnglish (US)
Pages (from-to)332-341
Number of pages10
JournalClinical Immunology
Volume105
Issue number3
DOIs
StatePublished - Dec 1 2002

Keywords

  • Autoimmunity
  • CD8 T cells
  • Epitopes
  • NOD mice
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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