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Adaptation by naïve CD4⁺ T cells to self-antigen–dependent TCR signaling induces functional heterogeneity and tolerance
by
Weiss, Arthur
, Zinzow-Kramer, Wendy M.
, Au-Yeung, Byron B.
in
Adaptation
/ Anergy
/ Animals
/ Antigens
/ Antigens, Ly - genetics
/ Antigens, Ly - immunology
/ Autoantigens
/ Autoantigens - genetics
/ Autoantigens - immunology
/ Biological Sciences
/ Cbl-b protein
/ CD4 antigen
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - drug effects
/ CD4-Positive T-Lymphocytes - immunology
/ CD5 antigen
/ CD5 Antigens - genetics
/ CD5 Antigens - immunology
/ Clonal Anergy
/ Gene Expression Regulation
/ Genes, Reporter
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - immunology
/ Heterogeneity
/ Immune Tolerance
/ Immunological tolerance
/ Immunology and Inflammation
/ Interleukin 2
/ Interleukin-2 - genetics
/ Interleukin-2 - immunology
/ Lymphocyte Activation - drug effects
/ Lymphocytes
/ Lymphocytes T
/ Major histocompatibility complex
/ Markers
/ Mice
/ Mice, Transgenic
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology
/ Nur77 protein
/ Ovalbumin - pharmacology
/ PD-1 protein
/ Peptides
/ Peptides - pharmacology
/ PNAS Plus
/ Receptors, Antigen, T-Cell - genetics
/ Receptors, Antigen, T-Cell - immunology
/ Signal strength
/ Signal Transduction
/ Signaling
/ Stimulation
/ T cell receptors
/ Tetradecanoylphorbol Acetate - pharmacology
2019
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Adaptation by naïve CD4⁺ T cells to self-antigen–dependent TCR signaling induces functional heterogeneity and tolerance
by
Weiss, Arthur
, Zinzow-Kramer, Wendy M.
, Au-Yeung, Byron B.
in
Adaptation
/ Anergy
/ Animals
/ Antigens
/ Antigens, Ly - genetics
/ Antigens, Ly - immunology
/ Autoantigens
/ Autoantigens - genetics
/ Autoantigens - immunology
/ Biological Sciences
/ Cbl-b protein
/ CD4 antigen
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - drug effects
/ CD4-Positive T-Lymphocytes - immunology
/ CD5 antigen
/ CD5 Antigens - genetics
/ CD5 Antigens - immunology
/ Clonal Anergy
/ Gene Expression Regulation
/ Genes, Reporter
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - immunology
/ Heterogeneity
/ Immune Tolerance
/ Immunological tolerance
/ Immunology and Inflammation
/ Interleukin 2
/ Interleukin-2 - genetics
/ Interleukin-2 - immunology
/ Lymphocyte Activation - drug effects
/ Lymphocytes
/ Lymphocytes T
/ Major histocompatibility complex
/ Markers
/ Mice
/ Mice, Transgenic
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology
/ Nur77 protein
/ Ovalbumin - pharmacology
/ PD-1 protein
/ Peptides
/ Peptides - pharmacology
/ PNAS Plus
/ Receptors, Antigen, T-Cell - genetics
/ Receptors, Antigen, T-Cell - immunology
/ Signal strength
/ Signal Transduction
/ Signaling
/ Stimulation
/ T cell receptors
/ Tetradecanoylphorbol Acetate - pharmacology
2019
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Adaptation by naïve CD4⁺ T cells to self-antigen–dependent TCR signaling induces functional heterogeneity and tolerance
by
Weiss, Arthur
, Zinzow-Kramer, Wendy M.
, Au-Yeung, Byron B.
in
Adaptation
/ Anergy
/ Animals
/ Antigens
/ Antigens, Ly - genetics
/ Antigens, Ly - immunology
/ Autoantigens
/ Autoantigens - genetics
/ Autoantigens - immunology
/ Biological Sciences
/ Cbl-b protein
/ CD4 antigen
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - drug effects
/ CD4-Positive T-Lymphocytes - immunology
/ CD5 antigen
/ CD5 Antigens - genetics
/ CD5 Antigens - immunology
/ Clonal Anergy
/ Gene Expression Regulation
/ Genes, Reporter
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - immunology
/ Heterogeneity
/ Immune Tolerance
/ Immunological tolerance
/ Immunology and Inflammation
/ Interleukin 2
/ Interleukin-2 - genetics
/ Interleukin-2 - immunology
/ Lymphocyte Activation - drug effects
/ Lymphocytes
/ Lymphocytes T
/ Major histocompatibility complex
/ Markers
/ Mice
/ Mice, Transgenic
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology
/ Nur77 protein
/ Ovalbumin - pharmacology
/ PD-1 protein
/ Peptides
/ Peptides - pharmacology
/ PNAS Plus
/ Receptors, Antigen, T-Cell - genetics
/ Receptors, Antigen, T-Cell - immunology
/ Signal strength
/ Signal Transduction
/ Signaling
/ Stimulation
/ T cell receptors
/ Tetradecanoylphorbol Acetate - pharmacology
2019
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Adaptation by naïve CD4⁺ T cells to self-antigen–dependent TCR signaling induces functional heterogeneity and tolerance
Journal Article
Adaptation by naïve CD4⁺ T cells to self-antigen–dependent TCR signaling induces functional heterogeneity and tolerance
2019
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Overview
Naïve CD4⁺ T cells experience weak T cell receptor (TCR) signals induced by self-peptides presented by MHC II. To investigate how these “basal” TCR signals influence responses to agonist TCR ligand stimulation, we analyzed naïve CD4⁺ cells expressing varying amounts of CD5, Ly6C, and Nur77-GFP, markers that reflect the strength of basal TCR signaling. Phenotypic analyses indicate that the broadest range of basal TCR signal strength can be visualized by a combination of Nur77-GFP and Ly6C. A range of basal TCR signaling is detectable even in populations that express identical TCRs. Whereas moderate basal TCR signal strength correlates with higher IL-2 secretion at early time points following TCR stimulation, weak basal TCR signaling correlated with higher IL-2 secretion at later time points. We identify a population of Nur77-GFPHI Ly6C⁻ cells that could not be reliably marked by either of CD5, Ly6C, or Nur77-GFP alone. These cells experience the strongest basal TCR signaling, consistently produce less IL-2, and express PD-1 and markers associated with anergy, such as Grail and Cbl-b. We propose that adaptation to the strength of basal TCR signaling drives the phenotypic and functional heterogeneity of naïve CD4⁺ cells.
Publisher
National Academy of Sciences
Subject
/ Anergy
/ Animals
/ Antigens
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - drug effects
/ CD4-Positive T-Lymphocytes - immunology
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - immunology
/ Lymphocyte Activation - drug effects
/ Major histocompatibility complex
/ Markers
/ Mice
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
/ Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology
/ Peptides
/ Receptors, Antigen, T-Cell - genetics
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