HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design
Abstract 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 huma...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01069-1 |
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| author | Amy L. Kessler Roel F. A. Pieterman Wouter A. S. Doff Karel Bezstarosti Rachid Bouzid Kim Klarenaar Diahann T. S. L. Jansen Robbie J. Luijten Jeroen A. A. Demmers Sonja I. Buschow |
| author_facet | Amy L. Kessler Roel F. A. Pieterman Wouter A. S. Doff Karel Bezstarosti Rachid Bouzid Kim Klarenaar Diahann T. S. L. Jansen Robbie J. Luijten Jeroen A. A. Demmers Sonja I. Buschow |
| author_sort | Amy L. Kessler |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-6b32f6ab62d54df6af5b45a02f5f804f |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-6b32f6ab62d54df6af5b45a02f5f804f2025-01-19T12:09:20ZengNature Portfolionpj Vaccines2059-01052025-01-0110111310.1038/s41541-025-01069-1HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine designAmy L. Kessler0Roel F. A. Pieterman1Wouter A. S. Doff2Karel Bezstarosti3Rachid Bouzid4Kim Klarenaar5Diahann T. S. L. Jansen6Robbie J. Luijten7Jeroen A. A. Demmers8Sonja I. Buschow9Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center RotterdamDepartment of Gastroenterology & Hepatology, Erasmus MC University Medical Center RotterdamProteomics Center, Department of Biochemistry, Erasmus MC University Medical Center RotterdamProteomics Center, Department of Biochemistry, Erasmus MC University Medical Center RotterdamDepartment of Gastroenterology & Hepatology, Erasmus MC University Medical Center RotterdamDepartment of Gastroenterology & Hepatology, Erasmus MC University Medical Center RotterdamDepartment of Gastroenterology & Hepatology, Erasmus MC University Medical Center RotterdamDepartment of Gastroenterology & Hepatology, Erasmus MC University Medical Center RotterdamProteomics Center, Department of Biochemistry, Erasmus MC University Medical Center RotterdamDepartment of Gastroenterology & Hepatology, Erasmus MC University Medical Center RotterdamAbstract 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.https://doi.org/10.1038/s41541-025-01069-1 |
| spellingShingle | Amy L. Kessler Roel F. A. Pieterman Wouter A. S. Doff Karel Bezstarosti Rachid Bouzid Kim Klarenaar Diahann T. S. L. Jansen Robbie J. Luijten Jeroen A. A. Demmers Sonja I. Buschow HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design npj Vaccines |
| title | HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design |
| title_full | HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design |
| title_fullStr | HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design |
| title_full_unstemmed | HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design |
| title_short | HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design |
| title_sort | hla i immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design |
| url | https://doi.org/10.1038/s41541-025-01069-1 |
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