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Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
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2012 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 42, no 3, 598-606 p.Article in journal (Refereed) Published
Abstract [en]

Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross-presentation of antigen to CD8+ T cells. Mice with hapten-specific circulating antibodies, but naϊve for the T-cell antigen, were infused with haptenated antigen and CD8+ T-cell induction was measured. Mice with circulating hapten-specific antibodies showed significantly enhanced cross-presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross-presentation in mice with circulating antigen-specific antibodies was associated with improved antigen capture by APCs. Importantly, CD11c+ APCs were responsible for the enhanced and sustained cross-presentation, although CD11c APCs had initially captured a significant amount of the injected antigen. Thus, in vivo formation of antigen-antibody immune complexes improves MHC class I cross-presentation, and CD8+ T-cell activation, demonstrating that humoral immunity can aid the initiation of systemic cellular immunity. These findings have important implications for the understanding of the action of therapeutic antibodies against tumor-associated antigens intensively used in the clinic nowadays.

Place, publisher, year, edition, pages
2012. Vol. 42, no 3, 598-606 p.
National Category
Immunology in the medical area
URN: urn:nbn:se:uu:diva-187543DOI: 10.1002/eji.201141613PubMedID: 22488363OAI: oai:DiVA.org:uu-187543DiVA: diva2:575101

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Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2015-03-01

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Mangsbo, Sara M
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