Key Points
MHC-II recycling through early endosomes in mature DCs is regulated by Rab11a.
MHC-II synthesis enhances presentation of late endosome Ags by immature DCs.
MHC-II recycling enhances presentation of early endosome Ags by mature DCs.
Abstract
Both immature and mature dendritic cells (DCs) can process and present foreign Ags to CD4 T cells; however, the mechanism by which MHC class II (MHC-II) in mature DCs acquires antigenic peptides remains unknown. To address this, we have studied Ag processing and presentation of two distinct CD4 T cell epitopes of the influenza virus hemagglutinin coat protein by both immature and mature mouse DCs. We find that immature DCs almost exclusively use newly synthesized MHC-II targeted to DM+ late endosomes for presentation to influenza virus–specific CD4 T cells. By contrast, mature DCs exclusively use recycling MHC-II that traffics to both early and late endosomes for antigenic peptide binding. Rab11a knockdown partially inhibits recycling of MHC-II in mature DCs and selectively inhibits presentation of an influenza virus hemagglutinin CD4 T cell epitope generated in early endosomes. These studies highlight a “division of labor” in MHC-II peptide binding, in which immature DCs preferentially present Ags acquired in Rab11a− DM+ late endosomes, whereas mature DCs use recycling MHC-II to present antigenic peptides acquired in both Rab11a+ early endosomes and Rab11a− endosomes for CD4 T cell activation.
Footnotes
This work was supported by a National Institutes of Health grant (to L.C.E.) and the Intramural Research Program of the National Institutes of Health (to P.A.R.).
The online version of this article contains supplemental material.
- Received October 23, 2019.
- Accepted December 31, 2019.
- Copyright © 2020 by The American Association of Immunologists, Inc.
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.