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

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 AIRC-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. (C) 2002 Elsevier Science (USA).