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1. Lattice Light-Sheet Microscopy Multi-dimensional Analyses (LaMDA) of T-Cell Receptor Dynamics Predict T-Cell Signaling States

   https://doi.org/10.1016/j.cels.2020.04.006  

   Rosenberg, Jillian ; Cao, Guoshuai ; Borja-Prieto, Fernanda ; Huang, Jun ( May 2020 , Cell Systems)
2. The molecular assembly of the marsupial γμ T cell receptor defines a third T cell lineage

   https://doi.org/10.1126/science.abe7070  

   Morrissey, Kimberly A. ; Wegrecki, Marcin ; Praveena, T. ; Hansen, Victoria L. ; Bu, Lijing ; Sivaraman, Komagal Kannan ; Darko, Samuel ; Douek, Daniel C. ; Rossjohn, Jamie ; Miller, Robert D. ; et al ( March 2021 , Science)

   αβ and γδ T cell receptors (TCRs) are highly diverse antigen receptors that define two evolutionarily conserved T cell lineages. We describe a population of γμTCRs found exclusively in non-eutherian mammals that consist of a two-domain (Vγ-Cγ) γ-chain paired to a three-domain (Vμ-Vμj-Cμ) μ-chain. γμTCRs were characterized by restricted diversity in the Vγ and Vμj domains and a highly diverse unpaired Vμ domain. Crystal structures of two distinct γμTCRs revealed the structural basis of the association of the γμTCR heterodimer. The Vμ domain shared the characteristics of a single-domain antibody within which the hypervariable CDR3μ loop suggests a major antigen recognition determinant. We define here the molecular basis underpinning the assembly of a third TCR lineage, the γμTCR.
3. PhenoGraph and viSNE facilitate the identification of abnormal T-cell populations in routine clinical flow cytometric data: PHENOGRAPH AND VISNE FACILITATE THE IDENTIFICATION OF ABNORMAL T CELLS

   https://doi.org/10.1002/cyto.b.21588  

   DiGiuseppe, Joseph A. ; Cardinali, Jolene L. ; Rezuke, William N. ; Pe'er, Dana ( September 2018 , Cytometry Part B: Clinical Cytometry)
4. Localized cytotoxic T cell–associated antigen 4 and antioxidant islet encapsulation alters macrophage signaling and induces regulatory and anergic T cells to enhance allograft survival

   https://doi.org/10.1016/j.ajt.2023.01.007  

   Barra, Jessie M. ; Kozlovskaya, Veronika ; Burnette, KaLia S. ; Banerjee, Ronadip R. ; Fraker, Christopher A. ; Kharlampieva, Eugenia ; Tse, Hubert M. ( April 2023 , American Journal of Transplantation)
5. A cell topography-based mechanism for ligand discrimination by the T cell receptor

   https://doi.org/10.1073/pnas.1817255116  

   Fernandes, Ricardo A. ; Ganzinger, Kristina A. ; Tzou, Justin C. ; Jönsson, Peter ; Lee, Steven F. ; Palayret, Matthieu ; Santos, Ana Mafalda ; Carr, Alexander R. ; Ponjavic, Aleks ; Chang, Veronica T. ; et al ( July 2019 , Proceedings of the National Academy of Sciences)

   The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of knownmore »agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes.« less