Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins
| Autor: | Evgeniy S. Egorov, Aleksandra M. Walczak, Mikhail V. Pogorelyy, Ekaterina A Komech, Elena I. Kovalenko, Dmitriy M. Chudakov, Anastasia A. Minervina, Ilgar Z. Mamedov, Yuri B. Lebedev, Thierry Mora, Anastasiia L. Sycheva, A Komkov, Maximilian Puelma Touzel, Galina G. Karganova |
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| Přispěvatelé: | Laboratoire de Physique Théorique de l'ENS (LPTENS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Statistique de l'ENS (LPS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] T-Lymphocytes T cell Receptors Antigen T-Cell Yellow fever vaccine chemical and pharmacologic phenomena Computational biology Biology DNA sequencing 03 medical and health sciences 0302 clinical medicine Immunology and Inflammation MESH: Antigens Viral/immunology medicine Humans Quantitative Biology - Populations and Evolution Antigens Viral 030304 developmental biology [PHYS]Physics [physics] 0303 health sciences Multidisciplinary RepSeq Physics Repertoire Vaccination Yellow Fever Vaccine T-cell receptor Populations and Evolution (q-bio.PE) high-throughput sequencing Twins Monozygotic twins Biological Sciences Tissue Donors 3. Good health MESH: Immunization/methods 030104 developmental biology medicine.anatomical_structure FOS: Biological sciences Physical Sciences Immunization T cell receptor Identical twins 030215 immunology medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2018, 115 (50), pp.12704-12709. ⟨10.1073/pnas.1809642115⟩ |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1809642115 |
| Popis: | Significance T cells play a key role in the adaptive immune system. The broad repertoire of unique receptors expressed by T cells is in principle able to recognize a huge diversity of pathogens, but how to extract that information from blood samples remains unclear. By sequencing and analyzing the statistics of T cell receptors of subjects vaccinated against yellow fever, we identified vaccine-specific receptors that expanded following vaccination. We show that each individual has a unique response, which is similar yet across subjects in its sequence composition, with a slightly higher similarity between twins. Our method can be used in the clinic to track disease-specific T cell clones expanding or contracting after infection, vaccination, or therapy. T cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 600 to 1,700 responding TCRs in each donor and validated them using three independent assays. While the responding TCRs were mostly private, albeit with higher overlap between twins, they could be well-predicted using a classifier based on sequence similarity. Our method can also be applied to samples obtained postinfection, making it suitable for systematic discovery of new infection-specific TCRs in the clinic. |
| Databáze: | OpenAIRE |
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