Differential uptake and cross-presentation of soluble and necrotic cell antigen by human DC subsets

Chiang, Meng-Chieh, Tullett, Kirsteen M., Lee, Yoke Seng, Idris, Adi, Ding, Yitian, McDonald, Kylie J., Kassianos, Andrew, Leal Rojas, Ingrid M., Jeet, Varinder, Lahoud, Mireille H. and Radford, Kristen J. (2015) Differential uptake and cross-presentation of soluble and necrotic cell antigen by human DC subsets. European Journal of Immunology, 46 2: 329-339. doi:10.1002/eji.201546023

Author Chiang, Meng-Chieh
Tullett, Kirsteen M.
Lee, Yoke Seng
Idris, Adi
Ding, Yitian
McDonald, Kylie J.
Kassianos, Andrew
Leal Rojas, Ingrid M.
Jeet, Varinder
Lahoud, Mireille H.
Radford, Kristen J.
Title Differential uptake and cross-presentation of soluble and necrotic cell antigen by human DC subsets
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 1521-4141
Publication date 2015
Sub-type Article (original research)
DOI 10.1002/eji.201546023
Open Access Status Not Open Access
Volume 46
Issue 2
Start page 329
End page 339
Total pages 11
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Collection year 2016
Language eng
Formatted abstract
Cross-presentation is the mechanism by which exogenous Ag is processed for recognition by CD8+ T cells. Murine CD8α+ DCs are specialized at cross-presenting soluble and cellular Ag, but in humans this process is poorly characterized. In this study, we examined uptake and cross-presentation of soluble and cellular Ag by human blood CD141+ DCs, the human equivalent of mouse CD8α+ DCs, and compared them with human monocyte-derived DCs (MoDCs) and blood CD1c+ DC subsets. MoDCs were superior in their capacity to internalize and cross-present soluble protein whereas CD141+ DCs were more efficient at ingesting and cross-presenting cellular Ag. Whilst cross-presentation by CD1c+ DCs and CD141+ DCs was dependent on the proteasome, and hence cytosolic translocation, cross-presentation by MoDCs was not. Inhibition of endosomal acidification enhanced cross-presentation by CD1c+ DCs and MoDCs but not by CD141+ DCs. These data demonstrate that CD1c+ DCs, CD141+ DCs, and MoDCs are capable of cross-presentation; however, they do so via different mechanisms. Moreover, they demonstrate that human CD141+ DCs, like their murine CD8α+ DC counterparts, are specialized at cross-presenting cellular Ag, most likely mediated by an enhanced capacity to ingest cellular Ag combined with subtle changes in lysosomal pH during Ag processing and use of the cytosolic pathway.
Keyword Antigen processing
Human dendritic cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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