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

ABSTRACT: Mucosal-associated invariant T (MAIT) cells are semi-invariant V?7.2+ CD161highCD4- 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 V?7.2+ CD161high T cell and related subset levels in infancy and after cord blood transplantation. We show that V?7.2+ and V?7.2- CD161high T cells are generated early during gestation and likely share a common prenatal developmental program. Among cord blood V?7.2+ CD161high 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 V?7.2+ CD161high T cells acquire a memory phenotype. Only these cells expand to form the adult MAIT pool, diluting out other V?7.2+ CD161high and V?7.2- CD161high 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 TCR?? chains recognizing MR1-restricted microbial antigens.

SUBMITTER: Ben Youssef G 

PROVIDER: S-EPMC5789419 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature