Expansion of the antigenic repertoire of a single T cell receptor upon T cell activation

Activated T cells and their naive precursors display different functional a vidities for peptide/MHC, but are thought to have identical antigenic reper toires. We show that, following activation with a cognate mimotope (NRP), d iabetogenic CD8(+) T cells expressing a single TCR (8.3) respond vigorously to numerous peptide analogs of NRP that were unable to elicit any response s from naive 8.3-CD8(+) T cells, even at high concentrations. The NRP-react ive, in vivo activated CD8(+) cells arising in pancreatic islets of nonobes e diabetic mice are similarly promiscuous for peptide/MHC, and paradoxicall y this promiscuity expands as the aviditiy of the T cell population for NRP /MHC increases with age. Thus, activation and avidity maturation of T lymph ocyte populations can lead to dramatic expansions in the range of peptides that elicit functional T cell responses.