دورية أكاديمية
Recruitment of epitope-specific T cell clones with a low-avidity threshold supports efficacy against mutational escape upon re-infection.
| العنوان: | Recruitment of epitope-specific T cell clones with a low-avidity threshold supports efficacy against mutational escape upon re-infection. |
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| المؤلفون: | Straub A; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany., Grassmann S; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany; The Joseph Sun Lab, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jarosch S; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany., Richter L; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany., Hilgendorf P; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany., Hammel M; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany., Wagner KI; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany., Buchholz VR; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany., Schober K; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany; Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; Medical Immunology Campus Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Schlossplatz 1, 91054 Erlangen, Germany. Electronic address: kilian.schober@uk-erlangen.de., Busch DH; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany; Partner site Munich, German Center for Infection Research (DZIF), Munich, Germany. Electronic address: dirk.busch@tum.de. |
| المصدر: | Immunity [Immunity] 2023 Jun 13; Vol. 56 (6), pp. 1269-1284.e6. Date of Electronic Publication: 2023 May 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
| مواضيع طبية MeSH: | CD8-Positive T-Lymphocytes* , Reinfection*, Humans ; Epitopes ; Receptors, Antigen, T-Cell/genetics ; Clone Cells ; Mutation/genetics |
| مستخلص: | Repetitive pathogen exposure leads to the dominant outgrowth of T cell clones with high T cell receptor (TCR) affinity to the relevant pathogen-associated antigens. However, low-affinity clones are also known to expand and form immunological memory. While these low-affinity clones contribute less immunity to the original pathogen, their role in protection against pathogens harboring immune escape mutations remains unclear. Based on identification of the TCR repertoire and functionality landscape of naive epitope-specific CD8 + T cells, we reconstructed defined repertoires that could be followed as polyclonal populations during immune responses in vivo. We found that selective clonal expansion is governed by clear TCR avidity thresholds. Simultaneously, initial recruitment of broad TCR repertoires provided a polyclonal niche from which flexible secondary responses to mutant epitopes could be recalled. Elucidating how T cell responses develop "from scratch" is informative for the development of enhanced immunotherapies and vaccines. Competing Interests: Declaration of interests D.H.B. is co-founder of STAGE Cell Therapeutics GmbH (now Juno Therapeutics/Celgene) and T Cell Factory B.V. (now Kite/Gilead). D.H.B. has a consulting contract with and receives sponsored research support from Juno Therapeutics/Celgene. (Copyright © 2023 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: TCR avidity; TCR repertoire; cross-reactivity; naive TCR repertoire; recruitment |
| المشرفين على المادة: | 0 (Epitopes) 0 (Receptors, Antigen, T-Cell) |
| تواريخ الأحداث: | Date Created: 20230510 Date Completed: 20230616 Latest Revision: 20230619 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.immuni.2023.04.010 |
| PMID: | 37164014 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4180 |
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| DOI: | 10.1016/j.immuni.2023.04.010 |