Abstract

Cross-presentation is the mechanism by which exogenous antigen is processed for recognition by CD8+ T cells. Murine CD8alpha+ DCs are specialised at cross-presenting soluble and cellular antigen but in humans this process is poorly characterised. In this study we examined uptake and cross-presentation of soluble and cellular antigen by human blood CD141+ DCs, the human equivalent of mouse CD8alpha+ DCs, and compared them with human MoDCs and blood CD1c+ DC subsets. MoDCs were superior in their capacity to internalise and cross-present soluble protein whereas CD141+ DCs were more efficient at ingesting and cross-presenting cellular antigen. 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 CD8alpha+ DC counterparts, are specialised at cross-presenting cellular antigen, most likely mediated by an enhanced capacity to ingest cellular antigen combined with subtle changes in lysosomal pH during Ag processing and use of the cytosolic pathway.

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