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. 2023 Feb 23;14:1127588. doi: 10.3389/fimmu.2023.1127588

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Copyright © 2023 Jabeen and Hinks

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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MAIT cell ontogeny. Mouse (top) and human (bottom) mucosal associated invariant T (MAIT) cell development follows three stages, largely within the thymus. Microbially derived 5-OP-RU is trafficked to the thymus and loaded onto MR1 expressed on double positive (DP) thymocytes. MAIT cells are subsequently positively selected on DP thymocytes in a process reliant upon signaling lymphocytic activation molecule (SLAM) interactions in mice (stage 1). During stage 2 and 3 MAIT cells acquire effector functions and their prototypic phenotype driven by PLZF expression. This occurs intrathymically in mice, but in human stage 3 can also occur peripherally. Distinguishing markers and important co-factors regulating differentiation are shown.