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Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Alberta, Canada;
Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia’s Children’s Hospital, Vancouver, British Columbia, Canada; and
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
Activated T cells and their naive precursors display different functional avidities for peptide/MHC, but are thought to have identical antigenic repertoires. We show that, following activation with a cognate mimotope (NRP), diabetogenic CD8+ T cells expressing a single TCR (8.3) respond vigorously to numerous peptide analogs of NRP that were unable to elicit any responses from naive 8.3-CD8+ T cells, even at high concentrations. The NRP-reactive, in vivo activated CD8+ cells arising in pancreatic islets of nonobese diabetic mice are similarly promiscuous for peptide/MHC, and paradoxically this promiscuity expands as the aviditiy of the T cell population for NRP/MHC increases with age. Thus, activation and avidity maturation of T lymphocyte populations can lead to dramatic expansions in the range of peptides that elicit functional T cell responses.
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