biostudies-literatureHuang YNCRR NIH HHSNIA NIH HHSNIAID NIH HHSNCI NIH HHS1086-95https://www.ebi.ac.uk/biostudies/studies/S-EPMC3197978biostudies-literatureUnknown12(11)The presence of immune memory at pathogen-entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the nonclassical major histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL), induced on dendritic cells interacting with CD8αα on activated CD8αβ(+) T cells, mediated affinity-based selection of memory precursor cells. Furthermore, constitutive expression of TL on epithelial cells led to continued selection of mature CD8αβ(+) memory T cells. The memory process driven by TL and CD8αα was essential for the generation of CD8αβ(+) memory T cells in the intestine and the accumulation of highly antigen-sensitive CD8αβ(+) memory T cells that form the first line of defense Nature immunologyMucosal memory CD8⁺ T cells are selected in the periphery by an MHC class I molecule.PMC3197978R01 CA156674T32 CA009385R01 AI064584R01 AI050265-09R01 AI050265-08R01 AI050265-07R56 AI050265R01 AI050265-06R01 AI064584-01R01 AG10152R01 AI064584-02R01 AI050265-05A1S10 RR027366R01 CA090571R01 AI064584-03R01 AI064584-04R01 AI050265R01 AI064584-05R01 AI064584-06R01 AI064584-07CA009385Herndler-Brandstetter DWang-Zhu YLarange AVan Kaer LArens RTeitell MASchoenberger SPGrubeck-Loebenstein BKronenberg MPark YHuang YAbraham NBernardo IOlivares-Villagomez DCheroutre HfalseMucosal memory CD8⁺ T cells are selected in the periphery by an MHC class I molecule.The presence of immune memory at pathogen-entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the nonclassical major histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL), induced on dendritic cells interacting with CD8αα on activated CD8αβ(+) T cells, mediated affinity-based selection of memory precursor cells. Furthermore, constitutive expression of TL on epithelial cells led to continued selection of mature CD8αβ(+) memory T cells. The memory process driven by TL and CD8αα was essential for the generation of CD8αβ(+) memory T cells in the intestine and the accumulation of highly antigen-sensitive CD8αβ(+) memory T cells that form the first line of defense 2011-01-01T00:00:00Z2011 Oct2025-04-04T07:57:35.983Z2019-03-27T00:45:14ZS-EPMC31979782196460910.1038/ni.2106