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Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo

Lookup NU author(s): Dr Ingrid Verhaart

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Abstract

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. Micewith hapten-specific circulating antibodies, but naïve 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.

Publication metadata

Author(s): van Montfoort N, Mangsbo SM, Camps MG, van Maren WW, Verhaart IE, Waisman A, Drijfhout JW, Melief CJ, Verbeek JS, Ossendorp F

Publication type: Article

Publication status: Published

Journal: European Journal of Immunology

Year: 2012

Volume: 42

Issue: 3

Pages: 598-606

Print publication date: 01/03/2012

Online publication date: 11/04/2012

ISSN (print): 0014-2980

ISSN (electronic): 1521-4141

Publisher: Wiley - VCH Verlag GmbH & Co. KGaA

URL: http://dx.doi.org/10.1002/eji.201141613

DOI: 10.1002/eji.201141613

PubMed id: 22488363

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