Advertisement

ResearchIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/JCI185443

A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant, trehalose monomycolate

Yuki Sakai,1 Minori Asa,1 Mika Hirose,2 Wakana Kusuhara,1 Nagatoshi Fujiwara,3 Hiroto Tamashima,4 Takahiro Ikazaki,4 Shiori Oka,5 Kota Kuraba,5 Kentaro Tanaka,6 Takashi Yoshiyama,7 Masamichi Nagae,1 Yoshihiko Hoshino,8 Daisuke Motooka,6 Ildiko Van Rhijn,9 Xiuyuan Lu,10 Eri Ishikawa,1 D. Branch Moody,9 Takayuki Kato,2 Shinsuke Inuki,5 Go Hirai,4 and Sho Yamasaki1

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Sakai, Y. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Asa, M. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Hirose, M. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Kusuhara, W. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Fujiwara, N. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Tamashima, H. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Ikazaki, T. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Oka, S. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Kuraba, K. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Tanaka, K. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Yoshiyama, T. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Nagae, M. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Hoshino, Y. in: JCI | PubMed | Google Scholar |

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Motooka, D. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Van Rhijn, I. in: JCI | PubMed | Google Scholar |

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Lu, X. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Ishikawa, E. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Moody, D. in: JCI | PubMed | Google Scholar |

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Kato, T. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Inuki, S. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Hirai, G. in: JCI | PubMed | Google Scholar

1Department of Molecular Immunology, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

2Laboratory of Cryo-EM Structural Biology, Institute for Protein Research, Osaka University, Suita, Japan

3Department of Food and Nutrition, Faculty of Contemporary Human Life Scienc, Tezukayama University, Nara, Japan

4Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

5Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

6Genome Information Research Center, Research Institute for Microbial Diseas, Osaka University, Suita, Japan

7Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

8Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Japan

9Division of Rheumatology, Immunity and Inflammation, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

10Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan

Find articles by Yamasaki, S. in: JCI | PubMed | Google Scholar |

Published December 24, 2024 - More info

J Clin Invest. https://doi.org/10.1172/JCI185443.
Copyright © 2024, Sakai et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 24, 2024 - Version history
View PDF
Abstract

Mycobacterium tuberculosis causes human tuberculosis. As mycobacteria are protected by thick lipid cell wall, humans have developed immune responses against diverse mycobacterial lipids. Most of these immunostimulatory lipids are known as adjuvants acting through innate immune receptors, such as C-type lectin receptors. Although a few mycobacterial lipid antigens activate unconventional T cells, antigenicity of most adjuvantic lipids are unknown. Here, we identified that trehalose monomycolate (TMM), an abundant mycobacterial adjuvant, activates human T cells bearing a unique ɑβTCR. This recognition was restricted by CD1b, a monomorphic antigen-presenting molecule conserved in primates but not mice. Single-cell TCR-RNA sequencing using newly established CD1b-TMM tetramers revealed that TMM-specific T cells are present as CD4+ effector memory T cells in the periphery of uninfected donors, but express IFNγ, TNF and anti-mycobacterial effectors upon TMM stimulation. TMM-specific T cells are detected in cord blood and PBMCs of non-BCG-vaccinated donors, but are expanded in active tuberculosis patients. A cryo-electron microscopy study of CD1b-TMM-TCR complexes revealed unique antigen recognition by conserved features of TCRs, positively-charged CDR3ɑ and long CDR3β regions. These results indicate that humans have a commonly-shared and pre-formed CD4+ T cell subset recognizing a typical mycobacterial adjuvant as an antigen. Furthermore, the dual role of TMM justifies reconsideration of the mechanism of action of adjuvants.

Graphical Abstract
graphical abstract
Supplemental material

View Unedited blot and gel images

View Supplementary video 1

View Supplementary video 2

View Supplementary video 3

View Validation report 8XUB

View Validation report 8ZOX

View

Version history
  • Version 1 (December 24, 2024): In-Press Preview
Advertisement
Advertisement