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Formation of Immune Complexes with a Tetanus-Derived B Cell Epitope Boosts Human T Cell Responses to Covalently Linked Peptides in an Ex Vivo Blood Loop System
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Immuneed AB, S-75237 Uppsala, Sweden.
Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands.
Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands.
Leiden Univ, Leiden Inst Chem, Dept Bioorgan Synth, NL-2300 RA Leiden, Netherlands.
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2018 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 201, no 1, p. 87-97Article in journal (Refereed) Published
Abstract [en]

Enhancing T cell responses against both viral and tumor Ags requires efficient costimulation and directed delivery of peptide Ags into APCs. Long peptide vaccines are considered favorable vaccine moieties from a clinical perspective, as they can harbor more than one immunogenic epitope enabling treatment of a broader target population. In addition, longer peptides are not extracellularly loaded on MHC class I; rather, they require intracellular processing and will thereby be presented to T cells mainly by professional APCs, thereby avoiding the risk of tolerance induction. The drawback of peptide vaccines regardless of peptide length is that naked peptides are not actively targeted to and taken up by APCs, and the standard nonconjugated adjuvant-peptide mixtures do not ensure cotargeting of the two to the same APC. We have identified a tetanus toxin-derived B cell epitope that can mediate the formation of immune complexes in the presence of circulating Abs. In this study, we show that these immune complexes improve both Ag uptake by APCs (blood monocytes and CD1c(+) dendritic cells) and consequently improve CD8(+) T cell recall responses in a human ex vivo blood loop system. The uptake of the peptide conjugate by blood monocytes is dependent on Abs and the complement component C1q. We envision that this strategy can be used to facilitate active uptake of Ags into APCs to improve T cell responses against pathogens or cancer.

Place, publisher, year, edition, pages
AMER ASSOC IMMUNOLOGISTS , 2018. Vol. 201, no 1, p. 87-97
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Immunology in the medical area
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URN: urn:nbn:se:uu:diva-364479DOI: 10.4049/jimmunol.1700911ISI: 000442387100011PubMedID: 29752315OAI: oai:DiVA.org:uu-364479DiVA, id: diva2:1259716
Funder
Swedish Research CouncilVINNOVASwedish Society for Medical Research (SSMF)Available from: 2018-10-30 Created: 2018-10-30 Last updated: 2018-10-30Bibliographically approved

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Fletcher, ErikaCodee, Jeroen D. C.Mangsbo, Sara
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