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

Nicole M. Kretzer, Derek J. Theisen, Roxane Tussiwand, Carlos G. Briseño, Gary E. Grajales-Reyes, Xiaodi Wu, Vivek Durai, Jörn Albring, Prachi Bagadia, Theresa L. Murphy, Kenneth M. Murphy

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Abstract

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.

Original languageEnglish
Pages (from-to)2871-2883
Number of pages13
JournalJournal of Experimental Medicine
Volume213
Issue number13
DOIs
StatePublished - Dec 12 2016

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    Kretzer, N. M., Theisen, D. J., Tussiwand, R., Briseño, C. G., Grajales-Reyes, G. E., Wu, X., Durai, V., Albring, J., Bagadia, P., Murphy, T. L., & Murphy, K. M. (2016). RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells. Journal of Experimental Medicine, 213(13), 2871-2883. https://doi.org/10.1084/jem.20160597