Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells-Reference-Cited by-同舟云学术

Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells

Published:2024-05-10 Issue:95 Volume:9 Page:
ISSN:2470-9468
Container-title:Science Immunology
language:en
Short-container-title:Sci. Immunol.

Author:

Vacchini Alessandro¹^ORCID,Chancellor Andrew¹^ORCID,Yang Qinmei¹,Colombo Rodrigo¹^ORCID,Spagnuolo Julian¹,Berloffa Giuliano¹^ORCID,Joss Daniel²,Øyås Ove³^ORCID,Lecchi Chiara⁴^ORCID,De Simone Giulia⁵^ORCID,Beshirova Aisha¹^ORCID,Nosi Vladimir¹^ORCID,Loureiro José Pedro¹^ORCID,Morabito Aurelia⁵^ORCID,De Gregorio Corinne¹^ORCID,Pfeffer Michael²^ORCID,Schaefer Verena¹^ORCID,Prota Gennaro¹,Zippelius Alfred⁶^ORCID,Stelling Jörg³^ORCID,Häussinger Daniel²^ORCID,Brunelli Laura⁵,Villalta Peter⁴⁷^ORCID,Lepore Marco¹^ORCID,Davoli Enrico⁵,Balbo Silvia⁴^ORCID,Mori Lucia¹,De Libero Gennaro¹^ORCID

Affiliation:

1. Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.

2. Department of Chemistry, University of Basel, Basel 4056, Switzerland.

3. Department of Biosystems Science and Engineering and SIB Swiss Institute of Bioinformatics, ETH Zurich, Basel 4058, Switzerland.

4. Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.

5. Department of Environmental Health Science, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano 20156, Italy.

6. Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.

7. Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciimmunol.adn0126

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