Novel ZAP-70-Related Immunodeficiency Presenting with Epstein–Barr Virus Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis

Forster, Moriah; Moran, Timothy P.; Beaven, Anne; Voorhees, Timothy J.

doi:10.1155/2021/6587323

Cited by 2 publications

(1 citation statement)

References 20 publications

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“…The TCR/ CD3 complex of traditional T cells recognizes specific antigens that bind to MHC and initiates the T cell activation (42,43). Tyrosine kinases such as Lck and ZAP70 participate in the downstream T cell activation signaling pathway after the CD3ϵ chain (44,45) of the T cell receptor is engaged. Furthermore, T cells were sub-clustered into specific 3 subsets (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome

et al. 2021

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Fish is considered as a supreme model for clarifying the evolution and regulatory mechanism of vertebrate immunity. However, the knowledge of distinct immune cell populations in fish is still limited, and further development of techniques advancing the identification of fish immune cell populations and their functions are required. Single cell RNA-seq (scRNA-seq) has provided a new approach for effective in-depth identification and characterization of cell subpopulations. Current approaches for scRNA-seq data analysis usually rely on comparison with a reference genome and hence are not suited for samples without any reference genome, which is currently very common in fish research. Here, we present an alternative, i.e. scRNA-seq data analysis with a full-length transcriptome as a reference, and evaluate this approach on samples from Epinephelus coioides-a teleost without any published genome. We show that it reconstructs well most of the present transcripts in the scRNA-seq data achieving a sensitivity equivalent to approaches relying on genome alignments of related species. Based on cell heterogeneity and known markers, we characterized four cell types: T cells, B cells, monocytes/macrophages (Mo/MΦ) and NCC (non-specific cytotoxic cells). Further analysis indicated the presence of two subsets of Mo/MΦ including M1 and M2 type, as well as four subsets in B cells, i.e. mature B cells, immature B cells, pre B cells and early-pre B cells. Our research will provide new clues for understanding biological characteristics, development and function of immune cell populations of teleost. Furthermore, our approach provides a reliable alternative for scRNA-seq data analysis in teleost for which no reference genome is currently available.

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Section: Discussionmentioning

confidence: 99%

Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome

et al. 2021

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Regulating the discriminatory response to antigen by T-cell receptor

et al. 2022

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The cell-mediated immune response constitutes a robust host defense mechanism to eliminate pathogens and oncogenic cells. T-cells play a central role in such a defense mechanism and creating memories to prevent any potential infection. T-cell recognizes foreign antigen by its surface receptors when presented through antigen-presenting cells and calibrates its cellular response by a network of intracellular signaling events. Activation of T-cell receptor (TCR) leads to changes in gene expression and metabolic networks regulating cell development, proliferation, and migration. TCR does not possess any catalytic activity, and the signaling initiates with the colocalization of several enzymes and scaffold proteins. Deregulation of T cell signaling is often linked to autoimmune disorders like SCID, Rheumatoid arthritis, and multiple sclerosis. The TCR remarkably distinguishes the minor difference between self and non-self antigen through a kinetic proofreading mechanism. The output of TCR signaling is determined by the half-life of the receptor-antigen complex and the time taken to recruit and activate the downstream enzymes. A longer half-life of a non-self antigen receptor complex could initiate downstream signaling by activating associated enzymes. Whereas, the short-lived self-peptide receptor complex disassembles before the downstream enzymes are activated. Activation of TCR rewires the cellular metabolic response to aerobic glycolysis from oxidative phosphorylation. How does the early event in the TCR signaling cross-talk with the cellular metabolism is an open question. In this review, we have discussed the recent developments in understanding the regulation of TCR signaling, and then we reviewed the emerging role of metabolism in regulating T-cell function.

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Novel ZAP-70-Related Immunodeficiency Presenting with Epstein–Barr Virus Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis

Cited by 2 publications

References 20 publications

Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome

Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome

Regulating the discriminatory response to antigen by T-cell receptor

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