Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1, by distinct human dendritic cell populations Journal Article


Authors: Nagata, Y.; Ono, S.; Matsuo, M.; Gnjatic, S.; Valmori, D.; Ritter, G.; Garrett, W.; Old, L. J.; Mellman, I.
Article Title: Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1, by distinct human dendritic cell populations
Abstract: Dendritic cells (DCs) play a critical role in initiating antigen-specific immune responses, because they are able to capture exogenous antigens for presentation to naïve T cells on both MHC class I and II molecules. As such, DCs represent important elements in the development of vaccine therapy for cancer. Although DCs are known to present antigens from phagocytosed tumor cells or preprocessed peptides, we explored whether they might also present soluble recombinant NY-ESO-1, a well characterized cancer antigen. We compared the abilities of human monocyte-derived DCs and DCs derived in vitro from CD34-positive stem cells to present NY-ESO-1 epitopes to MHC class I-restricted cytotoxic T cells. Although monocyte-derived DCs did not efficiently cross-present free NY-ESO-1 protein, IgG-immune complexes containing NY-ESO-1 were avidly presented after uptake by Fcγ receptors (FcγRII). In contrast, CD34-derived DCs were unable to process either soluble or immune complexed NY-ESO-1, although they efficiently presented preprocessed NY-ESO-1 peptides. This difference did not necessarily correlate with endocytic capacity. Although monocyte-derived DCs exhibited greater fluid-phase uptake than CD34-derived DCs, the two populations did not differ with respect to their surprisingly limited capacity for Fcγ receptor-mediated endocytosis. These results indicate that monocyte-derived DCs will be easier to load by using protein antigen in vitro than CD34-derived DCs, and that the latter population exhibits a restricted ability to crosspresent soluble exogenous antigens.
Keywords: controlled study; unclassified drug; human cell; proteins; cells, cultured; complex formation; cd34 antigen; cancer immunotherapy; dendritic cell; membrane proteins; cell population; tumor antigen; stem cell; antigen presentation; dendritic cells; immune response; antigens, neoplasm; cancer vaccine; ny eso 1 antigen; recombinant antigen; cytotoxic t lymphocyte; stem cells; fc receptor; immunophenotyping; monocyte; monocytes; phagocytosis; macrophages; major histocompatibility complex; endocytosis; antigens, cd34; immunoglobulin g antibody; major histocompatibility antigen class 1; solubility; antigen antibody complex; humans; human; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 99
Issue: 16
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2002-08-06
Start Page: 10629
End Page: 10634
Language: English
DOI: 10.1073/pnas.112331099
PUBMED: 12138174
PROVIDER: scopus
PMCID: PMC124995
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Mitsutoshi Matsuo
    9 Matsuo
  2. Yasuhiro Nagata
    11 Nagata
  3. Sacha Gnjatic
    113 Gnjatic
  4. Gerd Ritter
    166 Ritter
  5. Lloyd J Old
    593 Old