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 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.
Treiner
Emmanuel
E
Laboratoire d'Immunologie and INSERM U520, Institut Curie, Paris 75005, France.
Duban
Livine
L
Bahram
Seiamak
S
Radosavljevic
Mirjana
M
Wanner
Valerie
V
Tilloy
Florence
F
Affaticati
Pierre
P
Gilfillan
Susan
S
Lantz
Olivier
O
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D005075:Biological Evolution; D002678:Chimera / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007376:Interleukin-2 / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012641:Selection, Genetic; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D011948:Receptors, Antigen, T-Cell; C045084:invariant chain