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    1. Immunology and Inflammation

    CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance

    Yu Li, Pablo Guaman Tipan ... Lauren IR Ehrlich
    Two-photon microscopy, combined with chemotaxis assays, synchronized thymocyte selection studies, and flow cytometry analyses, reveal that CCR4 and CCR7 promote medullary entry and central tolerance of immature and mature post-positive selection thymocyte subsets, respectively, with distinct outcomes for central tolerance.
    1. Cell Biology

    pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells

    Payam E Farahani, Xiaoyu Yang ... Jared E Toettcher
    pYtags are novel biosensors that can be used to measure the activity of a receptor tyrosine kinase of interest in live cells with high spatiotemporal resolution and are applied to reveal rapid activity dynamics of EGFR/ErbB2 signaling.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Stimulation of the catalytic activity of the tyrosine kinase Btk by the adaptor protein Grb2

    Laura M Nocka, Timothy J Eisen ... John Kuriyan
    The adaptor protein Grb2 is able to enhance the activity of the cytoplasmic tyrosine kinase Btk through a novel mechanism, revealing a new role for Grb2 in B-cell signaling.
    1. Immunology and Inflammation

    PTPN22 R620W gene editing in T cells enhances low-avidity TCR responses

    Warren Anderson, Fariba Barahmand-pour-Whitman ... David J Rawlings
    Gene editing to generate precisely matched primary human T cell populations demonstrates that the common autoimmune risk allele in the tyrosine phosphatase, PTPN22, promotes signaling in cells expressing a low-avidity, self-reactive TCR specific for a diabetes-associated self-antigen.
    1. Biochemistry and Chemical Biology

    High-throughput profiling of sequence recognition by tyrosine kinases and SH2 domains using bacterial peptide display

    Allyson Li, Rashmi Voleti ... Neel H Shah
    A high-throughput method to profile tyrosine kinases and phosphotyrosine recognition domains reveals new rules for sequence specificity and maps the effects of mutations on the recognition of tyrosine phosphorylation sites.
    1. Immunology and Inflammation

    The meningeal transcriptional response to traumatic brain injury and aging

    Ashley C Bolte, Daniel A Shapiro ... John R Lukens
    Transcriptional analyses provide an atlas of how traumatic brain injury and aging shape meningeal cell composition and gene expression.
    1. Immunology and Inflammation

    Cell-intrinsic ceramides determine T cell function during melanoma progression

    Matthias Hose, Anne Günther ... Wiebke Hansen
    Cell-intrinsic ceramide concentrations are involved in T cell differentiation and function.
    1. Immunology and Inflammation
    2. Physics of Living Systems

    Progressive enhancement of kinetic proofreading in T cell antigen discrimination from receptor activation to DAG generation

    Derek M Britain, Jason P Town, Orion David Weiner
    A light-controllable ligand is used to probe where in the signaling cascade T cells discriminate self from non-self.
    1. Evolutionary Biology
    2. Immunology and Inflammation

    Enhancing and inhibitory motifs regulate CD4 activity

    Mark S Lee, Peter J Tuohy ... Michael S Kuhns
    Eutherian CD4 evolved counterbalancing motifs in the extracellular, transmembrane, and intracellular domains that regulate CD4+ T cell responses to peptide antigens presented by class II MHC (pMHCII).
    1. Immunology and Inflammation

    Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation

    Jaime James, Yifei Chen ... Rikard Holmdahl
    PTPN22 function is regulated by reactive oxygen species, and redox regulation of PTPN22 impacts T-cell-dependent autoimmune inflammation.