Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress.

Abstract

Human mucosal-associated invariant T (MAIT) cells express the semi-invariant T cell receptor Vα7.2 and are restricted by the MHC-Ib molecule MR1. While MAIT cells share similarities with other innate T cells the extent to which MAIT cells are innate and their capacity to adapt is unknown. We evaluated the function of Vα7.2+ T cells from the thymus, cord blood, and peripheral blood. While antigen-inexperienced MAIT cells displayed a naive phenotype these had intrinsic effector capacity in response to Mycobacterium tuberculosis infected cells. Vα7.2+ effector thymocytes contained sjTREC suggesting limited replication and thymic origin. In evaluating the capacity of Mtb-reactive MAIT cells to adapt, we found that those from peripheral blood demonstrated a memory phenotype and had undergone substantial expansion suggesting they responded to antigenic stimulation. MAIT cells, an evolutionarily conserved T cell subset that detects a variety of intracellular infections, share features of innate and adaptive immunity.