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Diagnostics
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T-cells as a Diagnostic Tool in Benign and Malignant Disease
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T-cells as a Diagnostic Tool in Benign and Malignant Disease

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 6456

Special Issue Editor

Dr. Elizabeth Soilleux

E-Mail Website
Guest Editor
1. Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
2. Haematopathology and Oncology Diagnostic Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
3. Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
Interests: lymphoma; coeliac/celiac disease; T-cell receptor; B-cell receptor; T-cell receptor repertoire; B-cell receptor repertoire; clonality; molecular diagnostics; sequencing; immunohistochemistry; immunostaining; in situ hybridisation; digital image analysis; artificial intelligence; machine learning; autopsy; COVID-19; SARS-CoV-2; immunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

T-cells are lymphocytes that form the backbone of the adaptive immune system, playing key roles in immunological tolerance, responses to infection and keeping potentially neoplastic processes in check. Because of this, they are one of the most widely involved cell types in disease processes. Like all cells, various phenotypes can be defined, and T-cells have a broader range of immunophenotypic markers than many other cell types, allowing a number of categories to be defined with different roles, activation status and levels of dysfunction or exhaustion. In addition to the many, variably expressed immunophenotypic markers on the surface of T-cells, nature has provided an extraordinary system that permits us to follow T-cells in any body fluid or tissue. This is because each T-cell undertakes rearrangement of its DNA in between 2 and 4 gene loci (TRA, TRB, TRG and TRD), generating unique sequences in the alpha/beta or gamma/delta T-cell receptor, permitting unique antigen binding specificity. T-cells responding to antigens undergo clonal expansion, increasing the frequency of their particular receptor. In the rare event of the development of T-cell neoplasia (lymphoma), clonal expansion is even more marked. This Special Issue will consider how these extraordinary facets of T-cell biology have been exploited in the diagnosis of benign and malignant disease.

Dr. Elizabeth Soilleux
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • T-cell
  • lymphocyte
  • T-cell receptor
  • next-generation sequencing
  • immunohistochemistry
  • in situ hybridisation
  • patient classification
  • disease
  • diagnosis
  • gene rearrangement

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Published Papers (1 paper)

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20 pages, 1040 KiB  
Review
Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19
by Hannah Kockelbergh, Shelley Evans, Tong Deng, Ella Clyne, Anna Kyriakidou, Andreas Economou, Kim Ngan Luu Hoang, Stephen Woodmansey, Andrew Foers, Anna Fowler and Elizabeth J. Soilleux
Diagnostics 2022, 12(5), 1222; https://doi.org/10.3390/diagnostics12051222 - 13 May 2022
Cited by 9 | Viewed by 5652
Abstract
Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries [...] Read more.
Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights. Full article
(This article belongs to the Special Issue T-cells as a Diagnostic Tool in Benign and Malignant Disease)
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