Abstract
The low frequency of self-peptide-specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single-positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults. Postthymic replicative history of Melan-A/MART-1-specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo. We provide direct evidence that the large T cell pool specific for the self-antigen Melan-A/MART-1 is mostly generated by thymic output of a high number of precursors. This represents the only known naive self-peptide-specific T cell repertoire directly accessible in humans.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antigens, Neoplasm
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Autoantigens / immunology*
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Flow Cytometry
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Gene Rearrangement, T-Lymphocyte / genetics
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HLA-A2 Antigen / immunology
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Humans
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Immunologic Memory
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Infant, Newborn
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Lymphocyte Activation
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MART-1 Antigen
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Middle Aged
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Neoplasm Proteins / immunology*
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / immunology
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Stem Cells / cytology
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Stem Cells / immunology
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Telomere / genetics
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Thymus Gland / cytology*
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Thymus Gland / immunology*
Substances
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Antigens, Neoplasm
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Autoantigens
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HLA-A2 Antigen
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MART-1 Antigen
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MLANA protein, human
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Neoplasm Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta