Journal
SCIENCE IMMUNOLOGY
Volume 5, Issue 49, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abc9492
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Funding
- National Health and Medical Research Council of Australia (NHMRC) [1013667, 1016629]
- Targeted Call for Research grant (NHMRC) [1113531]
- Australian Research Council (ARC) [CE140100011, DP170102471]
- Division of Intramural Research, NIAID/NIH
- ARC Future Fellowship [FT160100074]
- NHMRC [1117766, 1154502]
- ARC DECRA Fellowships
- Australian ARC Laureate Fellowship
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI000615] Funding Source: NIH RePORTER
- National Health and Medical Research Council of Australia [1154502, 1117766] Funding Source: NHMRC
- Australian Research Council [FT160100074] Funding Source: Australian Research Council
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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. MR1(R9H) was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1(R9H) 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 MR1(R9H) 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 gamma delta T cell population, indicating a compensatory interplay between these unconventional T cell subsets.
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