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   https://doi.org/10.1126/sciadv.aaz7809  

   Rath, Jan A. ; Bajwa, Gagan ; Carreres, Benoit ; Hoyer, Elisabeth ; Gruber, Isabelle ; Martínez-Paniagua, Melisa A. ; Yu, Yi-Ru ; Nouraee, Nazila ; Sadeghi, Fatemeh ; Wu, Mengfen ; et al ( July 2020 , Science Advances)

   Transgenic coexpression of a class I–restricted tumor antigen–specific T cell receptor (TCR) and CD8αβ (TCR8) redirects antigen specificity of CD4 + T cells. Reinforcement of biophysical properties and early TCR signaling explain how redirected CD4 + T cells recognize target cells, but the transcriptional basis for their acquired antitumor function remains elusive. We, therefore, interrogated redirected human CD4 + and CD8 + T cells by single-cell RNA sequencing and characterized them experimentally in bulk and single-cell assays and a mouse xenograft model. TCR8 expression enhanced CD8 + T cell function and preserved less differentiated CD4 + and CD8 + T cells after tumor challenge. TCR8 + CD4 + T cells were most potent by activating multiple transcriptional programs associated with enhanced antitumor function. We found sustained activation of cytotoxicity, costimulation, oxidative phosphorylation– and proliferation-related genes, and simultaneously reduced differentiation and exhaustion. Our study identifies molecular features of TCR8 expression that can guide the development of enhanced immunotherapies. 

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2. pyTCR: A comprehensive and scalable solution for TCR-Seq data analysis to facilitate reproducibility and rigor of immunogenomics research

   https://doi.org/10.3389/fimmu.2022.954078  

   Peng, Kerui ; Moore, Jaden ; Vahed, Mohammad ; Brito, Jaqueline ; Kao, Guoyun ; Burkhardt, Amanda M. ; Alachkar, Houda ; Mangul, Serghei ( October 2022 , Frontiers in Immunology)

   T cell receptor (TCR) studies have grown substantially with the advancement in the sequencing techniques of T cell receptor repertoire sequencing (TCR-Seq). The analysis of the TCR-Seq data requires computational skills to run the computational analysis of TCR repertoire tools. However biomedical researchers with limited computational backgrounds face numerous obstacles to properly and efficiently utilizing bioinformatics tools for analyzing TCR-Seq data. Here we report pyTCR, a computational notebook-based solution for comprehensive and scalable TCR-Seq data analysis. Computational notebooks, which combine code, calculations, and visualization, are able to provide users with a high level of flexibility and transparency for the analysis. Additionally, computational notebooks are demonstrated to be user-friendly and suitable for researchers with limited computational skills. Our tool has a rich set of functionalities including various TCR metrics, statistical analysis, and customizable visualizations. The application of pyTCR on large and diverse TCR-Seq datasets will enable the effective analysis of large-scale TCR-Seq data with flexibility, and eventually facilitate new discoveries. 

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3. Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR-induced signaling and cytokine production

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4. GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells

   https://doi.org/10.1016/j.cellsig.2015.01.012  

   Bilal, Mahmood Y. ; Zhang, Elizabeth Y. ; Dinkel, Brittney ; Hardy, Daimon ; Yankee, Thomas M. ; Houtman, Jon C.D. ( April 2015 , Cellular Signalling)
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