Abstract
SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) nucleates a signaling complex critical for T-cell receptor (TCR) signal propagation. Mutations in the tyrosines of SLP-76 result in graded defects in TCR-induced signals depending on the tyrosine(s) affected. Here we use 2 strains of genomic knock-in mice expressing tyrosine to phenylalanine mutations to examine the role of TCR signals in the differentiation of effector and memory CD8(+) T cells in response to infection in vivo. Our data support a model in which altered TCR signals can determine the rate of memory versus effector cell differentiation independent of initial T-cell expansion. Furthermore, we show that TCR signals sufficient to promote CD8(+) T-cell differentiation are different from those required to elicit inflammatory cytokine production.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / physiology*
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Animals
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Blotting, Western
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / virology
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Cell Differentiation
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Cell Proliferation
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Flow Cytometry
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Immunologic Memory*
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Lymphocyte Activation
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / pathology
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Lymphocytic Choriomeningitis / virology
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Lymphocytic choriomeningitis virus / pathogenicity
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Mutation / genetics
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Phosphoproteins / physiology*
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Receptors, Antigen, T-Cell / physiology*
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Signal Transduction / physiology*
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Tyrosine / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Phosphoproteins
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Receptors, Antigen, T-Cell
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SLP-76 signal Transducing adaptor proteins
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Tyrosine