Abstract
The choice between the alphabeta or gammadelta T cell fates is influenced by the production of functional, in-frame rearrangements of the TCR genes, but the mechanism that controls the lineage choice is not known. Here, we show that T cells that are heterozygous for a mutation of the Notch1 gene are more likely to develop as gammadelta T cells than as alphabeta T cells, implying that reduced Notch activity favors the gammadelta T cell fate over the alphabeta T cell fate. A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gammadeltaTCR gene rearrangements to adopt the alphabeta T cell fate. Our data indicate that Notch acts together with the newly formed T cell antigen receptor to direct the alphabeta versus gammadelta T cell lineage decision.
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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CD4-Positive T-Lymphocytes / chemistry
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CD4-Positive T-Lymphocytes / cytology*
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CD4-Positive T-Lymphocytes / physiology
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CD8-Positive T-Lymphocytes / chemistry
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / physiology
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Cell Differentiation / physiology
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Cell Lineage / physiology
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Female
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Flow Cytometry
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Gene Dosage
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Gene Rearrangement
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Hematopoietic Stem Cells / immunology
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Heterozygote
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Male
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Membrane Proteins / genetics*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Polymerase Chain Reaction
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Polymorphism, Restriction Fragment Length
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Receptors, Antigen, T-Cell, alpha-beta / genetics*
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Receptors, Antigen, T-Cell, gamma-delta / genetics*
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Receptors, Notch
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Recombinant Fusion Proteins / immunology
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Signal Transduction / immunology
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Thymus Gland / cytology
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Thymus Gland / immunology
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Transgenes / immunology
Substances
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Membrane Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Notch
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Recombinant Fusion Proteins