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Plasmacytoid dendritic cells of melanoma patients present exogenous proteins to CD4⁺ T cells after FcRII-mediated uptake

¹ Department of Tumor Immunology, ² Department of Blood Transfusion and Transplantation Immunology, ³ Department of Medical Oncology, and ⁴ Department of Pediatric Oncology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, Netherlands
⁵ Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany

CORRESPONDENCE I. Jolanda M. de Vries: j.devries{at}ncmls.ru.nl

Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immune responses by producing type I interferons. Although human pDCs can induce T cell responses upon viral infection, it remains unclear if pDCs can present exogenous antigens. Here, we show that human pDCs exploit FcRII (CD32) to internalize antigen–antibody complexes, resulting in the presentation of exogenous antigen to T cells. pDCs isolated from melanoma patients vaccinated with autologous monocyte-derived peptide- and keyhold limpet hemocyanin (KLH)–loaded dendritic cells, but not from nonvaccinated patients or patients that lack a humoral response against KLH, were able to stimulate KLH-specific T cell proliferation. Interestingly, we observed that internalization of KLH by pDCs depended on the presence of serum from vaccinated patients that developed an anti-KLH antibody response. Anti-CD32 antibodies inhibited antigen uptake and presentation, demonstrating that circulating anti-KLH antibodies binding to CD32 mediate KLH internalization. We conclude that CD32 is an antigen uptake receptor on pDCs and that antigen presentation by pDCs is of particular relevance when circulating antibodies are present. Antigen presentation by pDCs may thus modulate the strength and quality of the secondary phase of an immune response.

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