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 H. Lahoud, Kristen J. Radford

Cross-presentation is the mechanism by which exogenous antigen is processed for recognition by CD8(+) T cells. Murine CD8α(+) 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 CD8α(+) 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 CD8α(+) 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. This article is protected by copyright. All rights reserved.