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Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells.
Vacchini, Alessandro; Chancellor, Andrew; Yang, Qinmei; Colombo, Rodrigo; Spagnuolo, Julian; Berloffa, Giuliano; Joss, Daniel; Øyås, Ove; Lecchi, Chiara; De Simone, Giulia; Beshirova, Aisha; Nosi, Vladimir; Loureiro, José Pedro; Morabito, Aurelia; De Gregorio, Corinne; Pfeffer, Michael; Schaefer, Verena; Prota, Gennaro; Zippelius, Alfred; Stelling, Jörg; Häussinger, Daniel; Brunelli, Laura; Villalta, Peter; Lepore, Marco; Davoli, Enrico; Balbo, Silvia; Mori, Lucia; De Libero, Gennaro.
Afiliação
  • Vacchini A; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Chancellor A; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Yang Q; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Colombo R; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Spagnuolo J; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Berloffa G; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Joss D; Department of Chemistry, University of Basel, Basel 4056, Switzerland.
  • Øyås O; Department of Biosystems Science and Engineering and SIB Swiss Institute of Bioinformatics, ETH Zurich, Basel 4058, Switzerland.
  • Lecchi C; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • De Simone G; Department of Environmental Health Science, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano 20156, Italy.
  • Beshirova A; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Nosi V; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Loureiro JP; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Morabito A; Department of Environmental Health Science, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano 20156, Italy.
  • De Gregorio C; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Pfeffer M; Department of Chemistry, University of Basel, Basel 4056, Switzerland.
  • Schaefer V; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Prota G; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Zippelius A; Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Stelling J; Department of Biosystems Science and Engineering and SIB Swiss Institute of Bioinformatics, ETH Zurich, Basel 4058, Switzerland.
  • Häussinger D; Department of Chemistry, University of Basel, Basel 4056, Switzerland.
  • Brunelli L; Department of Environmental Health Science, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano 20156, Italy.
  • Villalta P; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • Lepore M; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
  • Davoli E; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
  • Balbo S; Department of Environmental Health Science, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano 20156, Italy.
  • Mori L; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
  • De Libero G; Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
Sci Immunol ; 9(95): eadn0126, 2024 May 10.
Article em En | MEDLINE | ID: mdl-38728413
ABSTRACT
MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I-related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells, and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl-nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos de Histocompatibilidade Classe I / Antígenos de Histocompatibilidade Menor Limite: Animals / Humans Idioma: En Revista: Sci Immunol / Sci. immunol / Science immunology Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Suíça
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos de Histocompatibilidade Classe I / Antígenos de Histocompatibilidade Menor Limite: Animals / Humans Idioma: En Revista: Sci Immunol / Sci. immunol / Science immunology Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Suíça