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Antibodies engineered with IgD specificity efficiently deliver integrated T-cell epitopes for antigen presentation by B cells

Abstract

We have developed a strategy for improving the stimulation of T cells during immune responses by constructing recombinant antibodies that enhance the delivery of antigen to antigen-presenting cells, such as B cells. These antibodies have variable regions specific for surface molecules on B cells, and a constant region with an inserted antigen. In vitro, such antibodies make B cells approximately 1000-fold more efficient at presenting antigen and stimulating specific T cells. In vivo, the antibodies turn B cells of the spleen into potent stimulators of T cells. This approach may be useful for the generation of new vaccines.

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Figure 1: Strategy for efficient delivery of antigen (Ag) to antigen-presenting cell (APC).
Figure 2: Ability of recombinant Abs to induce T cell proliferation.
Figure 3: B cell requirement for the enhanced T-cell activation obtained with αIgD.L3.
Figure 4: Requirement of IgD expression on B cells for enhanced presentation of αIgD.L3.
Figure 5: In vivo targeting of αIgD.L3 to splenic B cells.
Figure 6: In vivo proliferation of TcR transgenic T cells in response to αIgD.L3.

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Acknowledgements

We thank Hilde Omholt and Peter Hofgaard for excellent technical assistance, Ingunn B. Rasmussen and Janne K. Eidem for helpful discussions, and Joel Glover for reading the manuscript. The work was supported by grants from The Norwegian Research Council and The Norwegian Cancer Society.

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Correspondence to Elin Lunde.

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Lunde, E., Munthe, L., Vabø, A. et al. Antibodies engineered with IgD specificity efficiently deliver integrated T-cell epitopes for antigen presentation by B cells. Nat Biotechnol 17, 670–675 (1999). https://doi.org/10.1038/10883

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