Rab11a Regulates MHC Class II Recycling and Promotes Antigenic Peptide Exchange in Recycling Endosomes of Mature Dendritic Cells

Abstract

Abstract Dendritic cells (DCs) specialize in antigen capture and maintain a highly dynamic pool of peptide-MHC class II complexes (MHC-II) that continuously internalized and degraded in immature DCs. By contrast, in mature DCs pMHC-II internalizes but is efficiently recycled back to the plasma membrane for recognition by CD4 T cells. Regulation of pMHC-II biosynthesis and degradation is essential for optimal DC function, however the molecular basis of pMHC-II recycling and the cellular machinery that orchestrates pMHC-II trafficking are incompletely understood. In the present study we found that internalized pMHC-II on mature DCs, but not immature DCs, colocalizes with the regulator of endosome recycling Rab11a. Using a lentivirus encoded shRNA, we show that Rab11a knock-down inhibits recycling of pMHC-II in mature DCs. Moreover, Rab11a knock-down results in the intracellular accumulation of internalized surface pMHC-II. We also show that Rab11a knock-down in mature DCs specifically inhibits presentation of a “recycling endosome” epitope of internalized influenza hemagglutinin only in mature DCs. Our study thus identifies Rab11a as an important regulator of pMHC-II recycling that can enhance presentation of certain antigenic peptides in mature DCs.