Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2⁺ CD161^highCD4⁻ 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 TCRαβ chains recognizing MR1-restricted microbial antigens.

粘膜相关不变T（MAIT）细胞是半不变的Vα7.2 ⁺ CD161^高CD4 ^- T细胞，可识别微生物核黄素前体衍生物，如MR1提出的5-OP-RU。成人血液中的人MAIT细胞丰富，而脐带血中的人MAIT细胞却很少。我们纵向研究了婴儿期和脐带血移植后的Vα7.2 ⁺ CD161^高T细胞及相关亚群水平。我们显示，Vα7.2 ⁺和Vα7.2 ^- CD161^高T细胞是在妊娠早期产生的，可能共享一个共同的产前发育程序。脐血中Vα7.2 ⁺ CD161^高T细胞是少数识别MR1：5-OP-RU的细胞，其TRAV / TRBV成分与成年MAIT细胞非常相似。在生命的几周内，只有MR1：5-OP-RU反应性Vα7.2 ⁺ CD161^高T细胞获得记忆表型。只有这些细胞膨胀，形成成人MAIT池，稀释了其他Vα7.2 ⁺ CD161^高和Vα7.2 ^- CD161^高的人群中，至少需要6年达到成人水平的过程。因此，成年MAIT细胞的高克隆大小是抗原驱动的，并且可能是由于识别MR1限制性微生物抗原的TCRαβ链的精细特异性所致。