Abstract
Cross-presentation by MHC class I molecules (MHC-I) is critical for priming of cytotoxic T cells. Peptides derived from cross-presented antigens can be loaded on MHC-I in the endoplasmic reticulum and in endocytic or phagocytic compartments of murine DCs. However, the origin of MHC-I in the latter compartments is poorly understood. Recently, Rab22-dependent MHC-I recycling through a Rab11+ compartment has been suggested to be implicated in cross-presentation. We have examined the existence of MHC-I recycling and the role of Arf6, described to regulate recycling in nonprofessional antigen presenting cells, in murine DCs. We confirm folded MHC-I accumulation in a juxtanuclear Rab11+ compartment and partially localize Arf6 to this compartment. MHC-I undergo fast recycling, however, both folded and unfolded internalized MHC-I fail to recycle to the Rab11+Arf6+ compartment. Therefore, the source of MHC-I molecules in DC endocytic compartments remains to be identified. Functionally, depletion of Arf6 compromises cross-presentation of immune complexes but not of soluble, phagocytosed or mannose receptor–targeted antigen, suggesting a role of Fc receptor–regulated Arf6 trafficking in cross-presentation of immune complexes.
- Received June 21, 2019.
- Revision received November 1, 2019.
- Accepted November 4, 2019.
- © 2019 Montealegre et al.
This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).