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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
The Journal of experimental medicine, 02/2018, Volume: 215, Issue: 2Journal Article
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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