Your browser doesn't support javascript.
loading
Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1.
Howson, Lauren J; Awad, Wael; von Borstel, Anouk; Lim, Hui Jing; McWilliam, Hamish E G; Sandoval-Romero, Maria L; Majumdar, Shamik; Hamzeh, Abdul Rezzak; Andrews, Thomas D; McDermott, David H; Murphy, Philip M; Le Nours, Jérôme; Mak, Jeffrey Y W; Liu, Ligong; Fairlie, David P; McCluskey, James; Villadangos, Jose A; Cook, Matthew C; Turner, Stephen J; Davey, Martin S; Ojaimi, Samar; Rossjohn, Jamie.
Afiliação
  • Howson LJ; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. jamie.rossjohn@monash.edu lauren.howson@monash.edu.
  • Awad W; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • von Borstel A; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
  • Lim HJ; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • McWilliam HEG; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
  • Sandoval-Romero ML; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
  • Majumdar S; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
  • Hamzeh AR; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Andrews TD; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
  • McDermott DH; Centre for Personalised Immunology, John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory, Australia.
  • Murphy PM; Department of Immunology, Canberra Hospital, Canberra, Australian Capital Territory, Australia.
  • Le Nours J; Centre for Personalised Immunology, John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory, Australia.
  • Mak JYW; Department of Immunology, Canberra Hospital, Canberra, Australian Capital Territory, Australia.
  • Liu L; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Fairlie DP; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
  • McCluskey J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Villadangos JA; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
  • Cook MC; Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Turner SJ; ARC Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland, Australia.
  • Davey MS; Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Ojaimi S; ARC Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland, Australia.
  • Rossjohn J; Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Sci Immunol ; 5(49)2020 07 24.
Article em En | MEDLINE | ID: mdl-32709702
ABSTRACT
The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1R9H was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1R9H crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1R9H could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded γδ T cell population, indicating a compensatory interplay between these unconventional T cell subsets.
Assuntos
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 / Células T Invariantes Associadas à Mucosa / Linfócitos Intraepiteliais / Doenças da Imunodeficiência Primária Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
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 / Células T Invariantes Associadas à Mucosa / Linfócitos Intraepiteliais / Doenças da Imunodeficiência Primária Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article