TY - JOUR
T1 - HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design
AU - Kessler, Amy L.
AU - Pieterman, Roel F.A.
AU - Doff, Wouter A.S.
AU - Bezstarosti, Karel
AU - Bouzid, Rachid
AU - Klarenaar, Kim
AU - Jansen, Diahann T.S.L.
AU - Luijten, Robbie J.
AU - Demmers, Jeroen A.A.
AU - Buschow, Sonja I.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/1/18
Y1 - 2025/1/18
N2 - Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.
AB - Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.
UR - http://www.scopus.com/inward/record.url?scp=85218271032&partnerID=8YFLogxK
U2 - 10.1038/s41541-025-01069-1
DO - 10.1038/s41541-025-01069-1
M3 - Article
AN - SCOPUS:85218271032
VL - 10
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 12
ER -