Advertisement

Modulation of TAP-dependent antigen compartmentalization during human monocyte-to-DC differentiation

Marius Döring, Hanna Blees, Nicole Koller, Sabine Tischer-Zimmermann, Mathias Müsken, Frederik Henrich, Jennifer Becker, Elena Grabski, Junxi Wang, Hans Janssen, Werner Zuschratter, Jacques Neefjes, Frank Klawonn, Britta Eiz-Vesper, Robert Tampé and Ulrich Kalinke

Key Points

  • TAP activity wanes during monocyte to-DC-differentiation, thus enabling efficient cytotoxic T lymphocyte stimulation.

  • In monocytes, TAP localizes to endosomes, and upon differentiation to DCs, it travels to the ER and lysosomes and shows decreased activity.

Abstract

Dendritic cells (DCs) take up antigen in the periphery, migrate to secondary lymphoid organs, and present processed antigen fragments to adaptive immune cells and thus prime antigen-specific immunity. During local inflammation, recirculating monocytes are recruited from blood to the inflamed tissue, where they differentiate to macrophages and DCs. In this study, we found that monocytes showed high transporter associated with antigen processing (TAP)–dependent peptide compartmentalization and that after antigen pulsing, they were not able to efficiently stimulate antigen-specific T lymphocytes. Nevertheless, upon in vitro differentiation to monocyte-derived DCs, TAP-dependent peptide compartmentalization as well as surface major histocompatibility complex I turnover decreased and the cells efficiently restimulated T lymphocytes. Although TAP-dependent peptide compartmentalization decreased during DC differentiation, TAP expression levels increased. Furthermore, TAP relocated from early endosomes in monocytes to the endoplasmic reticulum (ER) and lysosomal compartments in DCs. Collectively, these data are compatible with the model that during monocyte-to-DC differentiation, the subcellular relocation of TAP and the regulation of its activity assure spatiotemporal separation of local antigen uptake and processing by monocytes and efficient T-lymphocyte stimulation by DCs.

  • Submitted October 12, 2018.
  • Accepted February 13, 2019.
View Full Text