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

A Amrani; P Serra; J Yamanouchi; J D Trudeau; R Tan; J F Elliott; P Santamaria

doi:10.4049/jimmunol.167.2.655

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

J Immunol. 2001 Jul 15;167(2):655-66. doi: 10.4049/jimmunol.167.2.655.

Authors

A Amrani¹, P Serra, J Yamanouchi, J D Trudeau, R Tan, J F Elliott, P Santamaria

Affiliation

¹ Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.

PMID: 11441068
DOI: 10.4049/jimmunol.167.2.655

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Amino Acid Substitution / immunology
Animals
Antigens / metabolism*
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism*
CD8-Positive T-Lymphocytes / pathology
Calcium-Binding Proteins / agonists
Calcium-Binding Proteins / immunology
Calcium-Binding Proteins / metabolism
Cell Differentiation / immunology
Cells, Cultured
Clone Cells
Diabetes Mellitus, Type 1 / immunology
Diabetes Mellitus, Type 1 / pathology
Hybridomas
Interferon-gamma / metabolism
Interleukin-2 / metabolism
Islets of Langerhans / metabolism
Islets of Langerhans / pathology
Lymphocyte Activation* / immunology
Membrane Glycoproteins / agonists
Membrane Glycoproteins / immunology
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred NOD
Mice, Knockout
Mice, Transgenic
Molecular Sequence Data
Peptide Fragments / agonists
Peptide Fragments / immunology
Peptide Fragments / metabolism
Prediabetic State / immunology
Prediabetic State / pathology
Receptors, Antigen, T-Cell / metabolism*
Tumor Cells, Cultured

Substances

Antigens
Calcium-Binding Proteins
Interleukin-2
Membrane Glycoproteins
Peptide Fragments
Receptors, Antigen, T-Cell
Interferon-gamma