Rab6 regulates recycling and retrograde trafficking of MR1 molecules

Sci Rep. 2020 Nov 27;10(1):20778. doi: 10.1038/s41598-020-77563-4.

Abstract

Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset important in the early response to bacterial and viral lung pathogens. MAIT cells recognize bacterial small molecule metabolites presented on the Class I-like molecule MR1. As with other Class I and Class II molecules, MR1 can likely sample ligands in the intracellular environment through multiple cellular pathways. Rab6, a small GTPase that regulates a number of endosomal trafficking pathways including retrograde transport to the trans-Golgi network (TGN), is involved in the presentation of ligands from Mycobacterium tuberculosis (Mtb) to MAIT cells. The Rab6-mediated trafficking pathway contains endosomal compartments that share features with the Mtb intracellular compartment. Using inducible expression of MR1, this study demonstrates that Rab6 regulates the recycling of MR1 molecules from the cell surface through endosomal trafficking compartments to the TGN. This Rab6-dependent pool of recycled MR1, which is available for reloading with ligands from bacterial pathogens like Mtb, may be important for early recognition of infected cells by MAIT cells in the lung.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antigen Presentation
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Endosomes / immunology
  • Endosomes / metabolism
  • Gene Silencing
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunity, Innate
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism
  • Mucosal-Associated Invariant T Cells / microbiology
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • Promoter Regions, Genetic
  • Protein Transport
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / immunology
  • rab GTP-Binding Proteins / metabolism*
  • trans-Golgi Network / immunology
  • trans-Golgi Network / metabolism

Substances

  • Histocompatibility Antigens Class I
  • Ligands
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • Rab6 protein
  • rab GTP-Binding Proteins