Abstract
Whether a single major histocompatibility complex (MHC)-bound peptide can drive the positive selection of large numbers of T cells has been a controversial issue. A diverse population of self peptides was shown to be essential for the in vivo development of CD4 T cells. Mice in which all but 5 percent of MHC class II molecules were bound by a single peptide had wild-type numbers of CD4 T cells. However, when the diversity within this 5 percent was lost, CD4 T cell development was impaired. Blocking the major peptide-MHC complex in thymus organ culture had no effect on T cell development, indicating that positive selection occurred on the diverse peptides present at low levels. This requirement for peptide diversity indicates that the interaction between self peptides and T cell receptors during positive selection is highly specific.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen Presentation
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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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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Cells, Cultured
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Histocompatibility Antigens Class II / immunology*
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Histocompatibility Antigens Class II / metabolism
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Lymphocyte Activation
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Lymphocyte Culture Test, Mixed
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Mice
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Mice, Knockout
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Mice, Transgenic
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Peptides / immunology*
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Peptides / metabolism
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Receptors, Antigen, T-Cell / immunology*
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Recombinant Fusion Proteins / metabolism
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Spleen / immunology
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Thymus Gland / immunology
Substances
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Histocompatibility Antigens Class II
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Peptides
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins