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

Meng-Chieh Chiang, Kirsteen M. Tullett, Yoke Seng Lee, Adi Idris, Yitian Ding, Kylie J. McDonald, Andrew Kassianos, Ingrid M. Leal Rojas, Varinder Jeet, Mireille Lahoud, Kristen J. Radford

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    21 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)329-339
    Number of pages11
    JournalEuropean Journal of Immunology
    Volume46
    Issue number2
    DOIs
    Publication statusPublished - Feb 2016

    Keywords

    • antigen processing
    • cross-presentation
    • human dendritic cells

    Cite this

    Chiang, M-C., Tullett, K. M., Lee, Y. S., Idris, A., Ding, Y., McDonald, K. J., Kassianos, A., Leal Rojas, I. M., Jeet, V., Lahoud, M., & Radford, K. J. (2016). Differential uptake and cross-presentation of soluble and necrotic cell antigen by human DC subsets. European Journal of Immunology, 46(2), 329-339. https://doi.org/10.1002/eji.201546023