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A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires.

التفاصيل البيبلوغرافية
العنوان: A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires.
المؤلفون: Ceglia V; Baylor Institute for Immunology Research, Dallas, TX, United States.; Université Paris-Est Créteil, Sciences de la Vie et de la Santé, Créteil, France.; Vaccine Research Institute, INSERM, Unité U955, Institut Mondor de Recherche Biomédicale, Créteil, France., Kelley EJ; Translational Genomics Research Institute, Flagstaff, AZ, United States., Boyle AS; Translational Genomics Research Institute, Flagstaff, AZ, United States., Zurawski S; Baylor Institute for Immunology Research, Dallas, TX, United States.; Vaccine Research Institute, INSERM, Unité U955, Institut Mondor de Recherche Biomédicale, Créteil, France., Mead HL; Translational Genomics Research Institute, Flagstaff, AZ, United States., Harms CE; Translational Genomics Research Institute, Flagstaff, AZ, United States., Blanck JP; Baylor Institute for Immunology Research, Dallas, TX, United States., Flamar AL; Baylor Institute for Immunology Research, Dallas, TX, United States.; Université Paris-Est Créteil, Sciences de la Vie et de la Santé, Créteil, France.; Vaccine Research Institute, INSERM, Unité U955, Institut Mondor de Recherche Biomédicale, Créteil, France., Kirschman JH; Translational Genomics Research Institute, Flagstaff, AZ, United States., Ogongo P; Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States., Ernst JD; Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States., Levy Y; Université Paris-Est Créteil, Sciences de la Vie et de la Santé, Créteil, France.; Vaccine Research Institute, INSERM, Unité U955, Institut Mondor de Recherche Biomédicale, Créteil, France., Zurawski G; Baylor Institute for Immunology Research, Dallas, TX, United States.; Vaccine Research Institute, INSERM, Unité U955, Institut Mondor de Recherche Biomédicale, Créteil, France., Altin JA; Translational Genomics Research Institute, Flagstaff, AZ, United States.
المصدر: Frontiers in immunology [Front Immunol] 2021 Nov 30; Vol. 12, pp. 735584. Date of Electronic Publication: 2021 Nov 30 (Print Publication: 2021).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Cell Separation/*methods , Immunologic Techniques/*methods , Receptors, Antigen, T-Cell/*analysis , Receptors, Antigen, T-Cell/*immunology , T-Lymphocytes/*immunology, Humans
مستخلص: Common approaches for monitoring T cell responses are limited in their multiplexity and sensitivity. In contrast, deep sequencing of the T Cell Receptor (TCR) repertoire provides a global view that is limited only in terms of theoretical sensitivity due to the depth of available sampling; however, the assignment of antigen specificities within TCR repertoires has become a bottleneck. This study combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to show that homologous 'Clusters of Expanded TCRs (CETs)' can be confidently identified without cell isolation, and assigned to antigen against a background of non-specific clones. We show that clonotypes within each CET respond to the same epitope, and that protein antigens stimulate multiple CETs reactive to constituent peptides. Finally, we demonstrate the personalized assignment of antigen-specificity to rare clones within fully-diverse uncultured repertoires. The method presented here may be used to monitor T cell responses to vaccination and immunotherapy with high fidelity.
Competing Interests: VC, SZ, YL, and GZ are inventors on patent application WO2020193718. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Ceglia, Kelley, Boyle, Zurawski, Mead, Harms, Blanck, Flamar, Kirschman, Ogongo, Ernst, Levy, Zurawski and Altin.)
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معلومات مُعتمدة: R21 AI149311 United States AI NIAID NIH HHS; U19 AI111211 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: T cell receptor (TCR); T cell responses; TCR sequencing; dendritic cells; monoclonal antibodies; vaccines
المشرفين على المادة: 0 (Receptors, Antigen, T-Cell)
تواريخ الأحداث: Date Created: 20211217 Date Completed: 20220204 Latest Revision: 20221130
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8670329
DOI: 10.3389/fimmu.2021.735584
PMID: 34917073
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-3224
DOI:10.3389/fimmu.2021.735584