TY - JOUR T1 - The role of MHC class I recycling and Arf6 in cross-presentation by murine dendritic cells JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900464 VL - 2 IS - 6 SP - e201900464 AU - Sebastian Montealegre AU - Anastasia Abramova AU - Valerie Manceau AU - Anne-Floor de Kanter AU - Peter van Endert Y1 - 2019/12/01 UR - https://www.life-science-alliance.org/content/2/6/e201900464.abstract N2 - 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. ER -