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Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection.
Schober, Kilian; Voit, Florian; Grassmann, Simon; Müller, Thomas R; Eggert, Joel; Jarosch, Sebastian; Weißbrich, Bianca; Hoffmann, Patrick; Borkner, Lisa; Nio, Enzo; Fanchi, Lorenzo; Clouser, Christopher R; Radhakrishnan, Aditya; Mihatsch, Lorenz; Lückemeier, Philipp; Leube, Justin; Dössinger, Georg; Klein, Ludger; Neuenhahn, Michael; Oduro, Jennifer D; Cicin-Sain, Luka; Buchholz, Veit R; Busch, Dirk H.
Afiliação
  • Schober K; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany. kilian.schober@tum.de.
  • Voit F; 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.
  • Müller TR; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Eggert J; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
  • Jarosch S; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Weißbrich B; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Hoffmann P; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Borkner L; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Nio E; Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
  • Fanchi L; ENPICOM B.V., 's-Hertogenbosch, the Netherlands.
  • Clouser CR; ENPICOM B.V., 's-Hertogenbosch, the Netherlands.
  • Radhakrishnan A; Juno Therapeutics/Celgene, Seattle, WA, USA.
  • Mihatsch L; Juno Therapeutics/Celgene, Seattle, WA, USA.
  • Lückemeier P; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Leube J; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Dössinger G; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Klein L; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Neuenhahn M; Institute for Immunology, Ludwig-Maximilians-Universität, Munich, Germany.
  • Oduro JD; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Cicin-Sain L; Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
  • Buchholz VR; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
  • Busch DH; Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Nat Immunol ; 21(4): 434-441, 2020 04.
Article em En | MEDLINE | ID: mdl-32205883
Adaptive evolution is a key feature of T cell immunity. During acute immune responses, T cells harboring high-affinity T cell antigen receptors (TCRs) are preferentially expanded, but whether affinity maturation by clonal selection continues through the course of chronic infections remains unresolved. Here we investigated the evolution of the TCR repertoire and its affinity during the course of infection with cytomegalovirus, which elicits large T cell populations in humans and mice. Using single-cell and bulk TCR sequencing and structural affinity analyses of cytomegalovirus-specific T cells, and through the generation and in vivo monitoring of defined TCR repertoires, we found that the immunodominance of high-affinity T cell clones declined during the chronic infection phase, likely due to cellular senescence. These data showed that under conditions of chronic antigen exposure, low-affinity TCRs preferentially expanded within the TCR repertoire, with implications for immunotherapeutic strategies.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Antígenos de Linfócitos T / Linfócitos T / Infecções por Citomegalovirus Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Antígenos de Linfócitos T / Linfócitos T / Infecções por Citomegalovirus Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article