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

Abstract

Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2 + CD161 high 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 high T cell and related subset levels in infancy and after cord blood transplantation. We show that Vα7.2 + and Vα7.2 - CD161 high T cells are generated early during gestation and likely share a common prenatal developmental program. Among cord blood Vα7.2 + CD161 high 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 high T cells acquire a memory phenotype. Only these cells expand to form the adult MAIT pool, diluting out other Vα7.2 + CD161 high and Vα7.2 - CD161 high 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 αβ chains recognizing MR1- restricted microbial antigens.