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 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.
Amrani
A
A
Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Serra
P
P
Yamanouchi
J
J
Trudeau
J D
JD
Tan
R
R
Elliott
J F
JF
Santamaria
P
P
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology; D006825:Hybridomas; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D011236:Prediabetic State / Q000276:immunology / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000941:Antigens; D002135:Calcium-Binding Proteins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma