Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1
Abstract
The evolutionary conservation of T lymphocyte subsets bearing T-cell receptors (TCRs) using invariant alpha-chains is indicative of unique functions. CD1d-restricted natural killer T (NK-T) cells that express an invariant Valpha14 TCRalpha chain have been implicated in microbial and tumour responses, as well as in auto-immunity. Here we show that T cells that express the canonical hValpha7.2-Jalpha33 or mValpha19-Jalpha33 TCR rearrangement are preferentially located in the gut lamina propria of humans and mice, respectively, and are therefore genuine mucosal-associated invariant T (MAIT) cells. Selection and/or expansion of this population requires B lymphocytes, as MAIT cells are absent in B-cell-deficient patients and mice. In addition, we show that MAIT cells are selected and/or restricted by MR1, a monomorphic major histocompatibility complex class I-related molecule that is markedly conserved in diverse mammalian species. MAIT cells are not present in germ-free mice, indicating that commensal flora is required for their expansion in the gut lamina propria. This indicates that MAIT cells are probably involved in the host response at the site of pathogen entry, and may regulate intestinal B-cell activity.
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MAIT cell activation is restricted to the non-polymorphic MHC class I related protein (MR1) which can present bacterial vitamin B2 and B9 metabolites to MAIT cells.
“Their activation is restricted to the non-polymorphic MHC class I 442 related protein (MR1) which can present bacterial vitamin B2 and B9 metabolites to MAIT 443 cells(88).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [88]
MAIT cells are another population of unconventional T cells enriched in liver tissue.
“Mucosal-associated invariant T (MAIT) cells are another population of unconventional T cells 441 enriched in liver tissue.”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [88]
The microbiota is necessary for MAIT cells in the thymus, spleen, gut, skin, lungs, and liver.
“A comparison of mice housed in conventional specific-pathogen-free (SPF) conditions to germ-free (GF) animals confirmed previous observations that the microbiota is necessary for the presence of MAIT cells in the thymus, spleen, and gut (17, 18), and extended this requirement for MAIT cells in the skin, lungs, and liver (Fig. 1B).”
From MAIT cells are imprinted by the microbiota in early life and promote tissue repair (2019) · cites this paper as [17]
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- Authors
- Treiner, E., Duban, L., Bahram, S., Radosavljevic, M., Wanner, V., Tilloy, F., Affaticati, P., Gilfillan, S., & Lantz, O.
- Affiliations
- Inserm (FR)
- Washington University in St. Louis (US)
- Corresponding author
- Gilfillan, Susan
- Lantz, Olivier
- ORCID
- Venue
- Nature
- Published
- 2003-03-13
- Volume
- 422
- Issue
- 6928
- Pages
- 164-169
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2030817385
- Cited by
- 1,139
- References
- 4
- Citations by year
- 2026: 47 · 2025: 75 · 2024: 66 · 2023: 75 · 2022: 84 · 2021: 94 · 2020: 116 · 2019: 98 · 2018: 73 · 2017: 65 · 2016: 57 · 2015: 58 · 2014: 34 · 2013: 35 · 2012: 19
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Update notices
- erratum (2003-06-26)
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- mucosal-associated invariant T cells, MR1, B cells, commensal bacteria, germ-free mice, intestinal immunity
- MeSH terms
- Amino Acid Sequence, Animals, Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, B-Lymphocytes, Base Sequence, Chimera, Biological Evolution, Humans, Interleukin-2, Intestines, Lymphocyte Activation, Molecular Sequence Data, Receptors, Antigen, T-Cell, Selection, Genetic, Gene Rearrangement, T-Lymphocyte, Histocompatibility Antigens Class I, Minor Histocompatibility Antigens, T-Lymphocyte Subsets, Gene Deletion, Mice, Knockout, Immunity, Mucosal, Mice
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