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RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells.

J. Exp. Med.2016 Dec 12;213(13):2871-2883. Epub 2016 Nov 29
Nicole M Kretzer 1 , Derek J Theisen 1 , Roxane Tussiwand 2 , Carlos G Briseño 1 , Gary E Grajales-Reyes 1 , Xiaodi Wu 1 , Vivek Durai 1 , Jörn Albring 3 , Prachi Bagadia 1 , Theresa L Murphy 1 , Kenneth M Murphy 4
Nicole M Kretzer 1 , Derek J Theisen 1 , Roxane Tussiwand 2 , Carlos G Briseño 1 , Gary E Grajales-Reyes 1 , Xiaodi Wu 1 , Vivek Durai 1 , Jörn Albring 3 , Prachi Bagadia 1 , Theresa L Murphy 1 , Kenneth M Murphy 4
+ et al

[No authors listed]

Author information
  • 1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
  • 2 Department of Biomedicine, University of Basel, 4003 Basel, Switzerland.
  • 3 Department of Medicine A, Hematology and Oncology, University of Münster, Münster 48149, Germany.
  • 4 Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.

摘要


In this study, to examine cross-presentation by classical dendritic cells (DCs; cDCs), we evaluated the role of RAB43, a protein found to be selectively expressed by Batf3-dependent CD8α+ and CD103+ compared with other DC subsets and immune lineages. Using a specific monoclonal antibody, we localized RAB43 expression to the Golgi apparatus and LAMP1- cytoplasmic vesicles. Mice with germline or conditional deletion of Rab43 are viable and fertile and have normal development of cDCs but show a defect for in vivo and in vitro cross-presentation of cell-associated antigen. This defect is specific to cDCs, as Rab43-deficient monocyte-derived DCs showed no defect in cross-presentation of cell-associated antigen. These results suggest that RAB43 provides a specialized activity used in cross-presentation selectively by CD8α+ DCs but not other antigen-presenting cells.