Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1

Emmanuel Treiner; Livine Duban; Seiamak Bahram; Mirjana Radosavljevic; Valerie Wanner; Florence Tilloy; Pierre Affaticati; Susan Gilfillan; Olivier Lantz

doi:10.1038/nature01433

Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1

Nature. 2003 Mar 13;422(6928):164-9. doi: 10.1038/nature01433.

Authors

Emmanuel Treiner¹, Livine Duban, Seiamak Bahram, Mirjana Radosavljevic, Valerie Wanner, Florence Tilloy, Pierre Affaticati, Susan Gilfillan, Olivier Lantz

Affiliation

¹ Laboratoire d'Immunologie and INSERM U520, Institut Curie, Paris 75005, France.

PMID: 12634786
DOI: 10.1038/nature01433

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Antigens, Differentiation, B-Lymphocyte / immunology*
B-Lymphocytes / immunology*
B-Lymphocytes / metabolism
Base Sequence
Biological Evolution*
Chimera / genetics
Chimera / immunology
Gene Deletion
Gene Rearrangement, T-Lymphocyte / genetics
Gene Rearrangement, T-Lymphocyte / immunology
Histocompatibility Antigens Class I / genetics
Histocompatibility Antigens Class I / immunology*
Histocompatibility Antigens Class I / metabolism
Histocompatibility Antigens Class II / immunology*
Humans
Immunity, Mucosal*
Interleukin-2 / biosynthesis
Intestines / immunology
Lymphocyte Activation*
Mice
Mice, Knockout
Minor Histocompatibility Antigens
Molecular Sequence Data
Receptors, Antigen, T-Cell / chemistry
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / immunology
Selection, Genetic
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism

Substances

Antigens, Differentiation, B-Lymphocyte
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
Interleukin-2
MR1 protein, human
Minor Histocompatibility Antigens
Mr1 protein, mouse
Receptors, Antigen, T-Cell
invariant chain