Ontogeny of human mucosal-associated invariant T cells and related T cell subsets

Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2 CD161 CD4 T cells that recognize microbial riboflavin precursor derivatives such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood, but there are very few in cord blood. We longitudinally studied Vα7.2 CD161...

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Published inThe Journal of experimental medicine Vol. 215; no. 2; pp. 459 - 479
Main Authors Ben Youssef, Ghada, Tourret, Marie, Salou, Marion, Ghazarian, Liana, Houdouin, Véronique, Mondot, Stanislas, Mburu, Yvonne, Lambert, Marion, Azarnoush, Saba, Diana, Jean-Sébastien, Virlouvet, Anne-Laure, Peuchmaur, Michel, Schmitz, Thomas, Dalle, Jean-Hugues, Lantz, Olivier, Biran, Valérie, Caillat-Zucman, Sophie
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 05.02.2018
The Rockefeller University Press
Subjects
Antigens
Blood
Children
Cord blood
Dilution
Gestation
Immunological memory
Invariants
Life Sciences
Lymphocytes
Lymphocytes T
Memory cells
Microorganisms
Mucosa
Ontogeny
Phenotypes
Riboflavin
Transplantation
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Summary:Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2 CD161 CD4 T cells that recognize microbial riboflavin precursor derivatives such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood, but there are very few in cord blood. We longitudinally studied Vα7.2 CD161 T cell and related subset levels in infancy and after cord blood transplantation. We show that Vα7.2 and Vα7.2 CD161 T cells are generated early during gestation and likely share a common prenatal developmental program. Among cord blood Vα7.2 CD161 T cells, the minority recognizing MR1:5-OP-RU display a TRAV/TRBV repertoire very similar to adult MAIT cells. Within a few weeks of life, only the MR1:5-OP-RU reactive Vα7.2 CD161 T cells acquire a memory phenotype. Only these cells expand to form the adult MAIT pool, diluting out other Vα7.2 CD161 and Vα7.2 CD161 populations, in a process requiring at least 6 years to reach adult levels. Thus, the high clonal size of adult MAIT cells is antigen-driven and likely due to the fine specificity of the TCRαβ chains recognizing MR1-restricted microbial antigens.
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J.-H. Dalle, O. Lantz, and V. Biran contributed equally to this paper.
G. Ben Youssef, M. Tourret, M. Salou, and L. Ghazarian contributed equally to this paper.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20171739