TY - JOUR
T1 - RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells
AU - Kretzer, Nicole M.
AU - Theisen, Derek J.
AU - Tussiwand, Roxane
AU - Briseño, Carlos G.
AU - Grajales-Reyes, Gary E.
AU - Wu, Xiaodi
AU - Durai, Vivek
AU - Albring, Jörn
AU - Bagadia, Prachi
AU - Murphy, Theresa L.
AU - Murphy, Kenneth M.
N1 - Funding Information:
We would like to thank Michael White for blastocyst injection and generation of mouse chimeras, Wandy Beatty for electron microscopy and confocal microscopy, Dennis Oakley at the Washington University Center for Cellular Imaging for confocal microscopy, and the Alvin J. Siteman Cancer Center at Washington University in St. Louis School of Medicine for use of the Center for Biomedical Informatics and Multiplex Gene Analysis Genechip Core Facility. We would like to thank David Fremont and Chris Nelson for advice on protein production and Bernd Zinselmeyer for help with microscopy analysis. The RAB43-/-ES cell used for this research project was generated by the trans-National Institutes of Health Knockout Mouse Project (KOMP) and obtained from the KOMP Repository. This work was funded by the Howard Hughes Medical Institute. National Institutes of Health grants to Velocigene at Regeneron Inc. (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells for 8,500 genes in the KOMP Program and archived and distributed by the KOMP Repository at University of California, Davis and Children's Hospital Oakland Research Institute (U42RR024244). For more information or to obtain KOMP products go to www.komp.org.
Publisher Copyright:
© 2016 Kretzer et al.
PY - 2016/12/12
Y1 - 2016/12/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85008466302&partnerID=8YFLogxK
U2 - 10.1084/jem.20160597
DO - 10.1084/jem.20160597
M3 - Article
C2 - 27899443
AN - SCOPUS:85008466302
VL - 213
SP - 2871
EP - 2883
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 13
ER -