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

The evolutionary conservation of T lymphocyte subsets bearing T-cell receptors (TCRs) using invariant α-chains is indicative of unique functions. CD1d-restricted natural killer T (NK-T) cells that express an invariant Vα14 TCRα chain have been implicated in microbial and tumour responses, as well as...

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Bibliographic Details
Published in:Nature (London) 2003-03, Vol.422 (6928), p.164-169
Main Authors: Gilfillan, Susan, Lantz, Olivier, Treiner, Emmanuel, Duban, Livine, Bahram, Seiamak, Radosavljevic, Mirjana, Wanner, Valerie, Tilloy, Florence, Affaticati, Pierre
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antigens, Differentiation, B-Lymphocyte - immunology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Base Sequence
Biological and medical sciences
Biological Evolution
Cellular biology
Chimera - genetics
Chimera - immunology
Evolution
Fundamental and applied biological sciences. Psychology
Fundamental 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
Immunobiology
Immunology
Interleukin-2 - biosynthesis
Intestines - immunology
Leukocytes
Life Sciences
Lymphocyte Activation
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
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
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Summary:The evolutionary conservation of T lymphocyte subsets bearing T-cell receptors (TCRs) using invariant α-chains is indicative of unique functions. CD1d-restricted natural killer T (NK-T) cells that express an invariant Vα14 TCRα 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 hVα7.2-Jα33 or mVα19-Jα33 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature01433