Title

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

Document Type

Article

Publication Date

2002

Keywords

CD8-Positive-T-Lymphocytes, Cell-Line-Transformed, Clone-Cells, Diabetes-Mellitus-Insulin-Dependent, Epitopes, Histocompatibility-Antigens-Class-I, Insulin, Islets-of-Langerhans, Mice, Mice-Inbred-NOD, Mice-Transgenic, Prediabetic-State, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes-Cytotoxic

JAX Source

Clin Immunol 2002 Dec; 105(3):332-41.

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.