Journal article

Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1

Lauren J Howson, Wael Awad, Anouk von Borstel, Hui Jing Lim, Hamish EG McWilliam, Maria L Sandoval-Romero, Shamik Majumdar, Abdul Rezzak Hamzeh, Thomas D Andrews, David H McDermott, Philip M Murphy, Jerome Le Nours, Jeffrey YW Mak, Ligong Liu, David P Fairlie, James McCluskey, Jose A Villadangos, Matthew C Cook, Stephen J Turner, Martin S Davey Show all

Science Immunology | American Association for the Advancement of Science | Published : 2020


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 bi..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Targeted Call for Research grant (NHMRC)

Awarded by Australian Research Council (ARC)

Awarded by ARC Future Fellowship

Awarded by NHMRC

Funding Acknowledgements

This work was supported by a program grant from the National Health and Medical Research Council of Australia (NHMRC) (1013667 and 1016629), a Targeted Call for Research grant (NHMRC) (1113531), the Australian Research Council (ARC) (CE140100011 and DP170102471), and the Division of Intramural Research, NIAID/NIH. J.L.N. is supported by an ARC Future Fellowship (FT160100074), D.P.F. is supported by an NHMRC Senior Principal Research Fellowship (1117766), J.A.V. is supported by a NHMRC Principal Research Fellowship (1154502). M.S.D. and H.E.G.M. are supported by ARC DECRA Fellowships, and J.R. is supported by an Australian ARC Laureate Fellowship.