MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells

  • Huang S
  • Gilfillan S
  • Kim S
 et al. 
  • 83


    Mendeley users who have this article in their library.
  • 84


    Citations of this article.


Like CD1d-restricted iNKT cells, mucosal-associated invariant T cells (MAITs) are “innate” T cells that express a canonical TCRα 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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Shouxiong Huang

  • Susan Gilfillan

  • Sojung Kim

  • Bruce Thompson

  • Xiaoli Wang

  • Andrea J. Sant

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free