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Infection and Immunity, September 2001, p. 5716-5725, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5716-5725.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cholera Toxin B Subunit as a Carrier Molecule Promotes Antigen Presentation and Increases CD40 and CD86 Expression on Antigen-Presenting Cells

Annie George-Chandy, Kristina Eriksson,* Michael Lebens, Inger Nordström, Emma Schön, and Jan Holmgren

Department of Medical Microbiology and Immunology, Göteborg University, Göteborg, Sweden

Received 22 January 2001/Returned for modification 2 April 2001/Accepted 20 April 2001

Cholera toxin B subunit (CTB) is an efficient mucosal carrier molecule for the generation of mucosal antibody responses and/or induction of systemic T-cell tolerance to linked antigens. CTB binds with high affinity to GM1 ganglioside cell surface receptors. In this study, we evaluated how conjugation of a peptide or protein antigen to CTB by chemical coupling or genetic fusion influences the T-cell-activating capacity of different antigen-presenting cell (APC) subsets. Using an in vitro system in which antigen-pulsed APCs were incubated with antigen-specific, T-cell receptor-transgenic T cells, we found that the dose of antigen required for T-cell activation could be decreased >10,000-fold using CTB-conjugated compared to free antigen. In contrast, no beneficial effects were observed when CTB was simply admixed with antigen. CTB conjugation enhanced the antigen-presenting capacity not only of dendritic cells and B cells but also of macrophages, which expressed low levels of cell surface major histocompatibility complex (MHC) class II and were normally poor activators of naive T cells. Enhanced antigen-presenting activity by CTB-linked antigen resulted in both increased T-cell proliferation and increased interleukin-12 and gamma interferon secretion and was associated with up-regulation of CD40 and CD86 on the APC surface. These results imply that conjugation to CTB dramatically lowers the threshold concentration of antigen required for immune cell activation and also permits low-MHC II-expressing APCs to prime for a specific immune response.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, Guldhedsgatan 10A, 413 46 Göteborg, Sweden. Phone: 46-31-3424761. Fax: 46-31-820160. E-mail: kristina.eriksson{at}microbio.gu.se.

Infection and Immunity, September 2001, p. 5716-5725, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5716-5725.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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