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

J Exp Med. 2016 Dec 12;213(13):2871-2883. doi: 10.1084/jem.20160597. Epub 2016 Nov 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / immunology
  • CD8 Antigens / genetics
  • CD8 Antigens / immunology*
  • Dendritic Cells / immunology*
  • Gene Expression Regulation / immunology
  • Golgi Apparatus / genetics
  • Golgi Apparatus / immunology
  • Mice
  • Mice, Knockout
  • Monocytes / immunology*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / immunology*

Substances

  • Basic-Leucine Zipper Transcription Factors
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Repressor Proteins
  • SNFT protein, mouse
  • rab11 protein
  • rab GTP-Binding Proteins