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¹ Department of Pathology and Immunology, Washington University, St. Louis, MO 63110
² Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642
³ Laboratoire d'Immunologie and Institut National de la Santé et de la Recherche Médicale U520, Institut Curie, 75005 Paris, France

CORRESPONDENCE Ted H. Hansen: hansen{at}wustl.edu

Like CD1d-restricted iNKT cells, mucosal-associated invariant T cells (MAITs) are "innate" T cells that express a canonical TCR chain, have a memory phenotype, and rapidly secrete cytokines upon TCR ligation. Unlike iNKT cells, MAIT cells require the class Ib molecule MHC-related protein I (MR1), B cells, and gut flora for development and/or expansion, and they preferentially reside in the gut lamina propria. Evidence strongly suggests that MAIT cell activation is ligand-dependent, but the nature of MR1 ligand is unknown. In this study, we define a mechanism of endogenous antigen presentation by MR1 to MAIT cells. MAIT cell activation was dependent neither on a proteasome-processed ligand nor on the chaperoning by the MHC class I peptide loading complex. However, MAIT cell activation was enhanced by overexpression of MHC class II chaperones Ii and DM and was strikingly diminished by silencing endogenous Ii. Furthermore, inhibiting the acidification of the endocytic compartments reduced MR1 surface expression and ablated MAIT cell activation. The importance of the late endosome for MR1 antigen presentation was further corroborated by the localization of MR1 molecules in the multivesicular endosomes. These findings demonstrate that MR1 traffics through endocytic compartments, thereby allowing MAIT cells to sample both endocytosed and endogenous antigens.

© 2008 Huang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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• Huang, S., Martin, E., Kim, S., Yu, L., Soudais, C., Fremont, D. H., Lantz, O., Hansen, T. H. (2009). MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proc. Natl. Acad. Sci. USA 106: 8290-8295 [Abstract] [Full Text]  
• Shimamura, M., Huang, Y.-Y., Kobayashi, M., Goji, H. (2009). Altered production of immunoregulatory cytokines by invariant V{alpha}19 TCR-bearing cells dependent on the duration and intensity of TCR engagement. Int Immunol 21: 179-185 [Abstract] [Full Text]  
• Huang, S., Gilfillan, S., Kim, S., Thompson, B., Wang, X., Sant, A. J., Fremont, D. H., Lantz, O., Hansen, T. H. (2008). MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells. JCB 181: i11-i11 [Full Text]  

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