MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR α-chain, TRAV1-2. These cells comprise a T cell subset that recognizes and mediates host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis. Here, we sought to characterize development of circulating human MR1T cells as defined by MR1-5-OP-RU tetramer labeling and of the TRAV1-2⁺ MAIT cells defined by expression of TRAV1-2 and high expression of CD26 and CD161 (TRAV1-2⁺CD161⁺⁺CD26⁺⁺ cells). We analyzed postnatal expansion, maturation, and functionality of peripheral blood MR1-5-OP-RU tetramer⁺ MR1T cells in cohorts from three different geographic settings with different tuberculosis (TB) vaccination practices, levels of exposure to and infection with M. tuberculosis. Early after birth, frequencies of MR1-5-OP-RU tetramer⁺ MR1T cells increased rapidly by several fold. This coincided with the transition from a predominantly CD4⁺ and TRAV1-2⁻ population in neonates, to a predominantly TRAV1-2⁺CD161⁺⁺CD26⁺⁺ CD8⁺ population. We also observed that tetramer⁺ MR1T cells that expressed TNF upon mycobacterial stimulation were very low in neonates, but increased ~10-fold in the first year of life. These functional MR1T cells in all age groups were MR1-5-OP-RU tetramer⁺TRAV1-2⁺ and highly expressed CD161 and CD26, markers that appeared to signal phenotypic and functional maturation of this cell subset. This age-associated maturation was also marked by the loss of naïve T cell markers on tetramer⁺ TRAV1-2⁺ MR1T cells more rapidly than tetramer⁺TRAV1-2⁻ MR1T cells and non-MR1T cells. These data suggest that neonates have infrequent populations of MR1T cells with diverse phenotypic attributes; and that exposure to the environment rapidly and preferentially expands the MR1-5-OP-RU tetramer⁺TRAV1-2⁺ population of MR1T cells, which becomes the predominant population of functional MR1T cells early during childhood.

MR1限制性T（MR1T）细胞的定义是，它们识别由MHC 1类单态相关分子MR1呈现的代谢物抗原，MR1是哺乳动物物种中最保守的I类MHC相关分子。粘膜相关不变T（MAIT）细胞是表达不变TCRα链TRAV1-2的MR1T细胞的主要子集。这些细胞包含一个T细胞亚群，可识别和介导宿主对多种微生物病原体的免疫反应，包括结核分枝杆菌。在这里，我们试图表征由MR1-5-OP-RU四聚体标记定义的循环人类MR1T细胞和由TRAV1-2的表达以及CD26和CD161（TRAV1的高表达）定义的TRAV1-2 ⁺ MAIT细胞的发育。 2 ⁺ CD161 ⁺⁺ CD26 ⁺⁺单元）。我们分析了来自三个不同地理环境的人群的外周血MR1-5-OP-RU四聚体⁺ MR1T细胞的产后扩增，成熟度和功能，这些人群具有不同的结核病（TB）疫苗接种方法，接触和感染的水平结核分枝杆菌。出生后早期，MR1-5-OP-RU四聚体⁺ MR1T细胞的频率迅速增加了几倍。这正好与从主要CD4过渡⁺和TRAV1-2 ^-人口新生儿，到主要为TRAV1-2 ⁺ CD161 ⁺ CD26 ⁺⁺ CD8 ⁺群体。我们还观察到在分枝杆菌刺激下表达TNF的四聚体⁺ MR1T细胞在新生儿中非常低，但在生命的第一年增加了约10倍。所有年龄段的这些功能性MR1T细胞均为MR1-5-OP-RU四聚体⁺ TRAV1-2 ⁺以及高表达的CD161和CD26，这些标志物似乎表明该细胞亚群的表型和功能成熟。这种与年龄有关的成熟还以四聚体⁺ TRAV1-2 ⁺ MR1T细胞比四聚体⁺ TRAV1-2 ^- MR1T细胞和非MR1T细胞更快的幼稚T细胞标记丧失为特征。这些数据表明，新生儿很少出现具有多种表型特征的MR1T细胞。并且这种暴露于环境的速度迅速并优先扩展了MR1-5T细胞的MR1-5-OP-RU四聚体⁺ TRAV1-2 ⁺ MR1T细胞的群体，这成为儿童期早期功能性MR1T细胞的主要群体。