RT Journal Article
SR Electronic
T1 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
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 87
OP 97
DO 10.4049/jimmunol.1700911
VO 201
IS 1
A1 Fletcher, Erika A. K.
A1 van Maren, Wendy
A1 Cordfunke, Robert
A1 Dinkelaar, Jasper
A1 Codee, Jeroen D. C.
A1 van der Marel, Gijs
A1 Melief, Cornelis J. M.
A1 Ossendorp, Ferry
A1 Drijfhout, Jan Wouter
A1 Mangsbo, Sara M.
YR 2018
UL http://www.jimmunol.org/content/201/1/87.abstract
AB 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.This article is featured in In This Issue, p.3