HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design

被引:2
作者
Kessler, Amy L. [1 ,3 ,4 ]
Pieterman, Roel F. A. [1 ]
Doff, Wouter A. S. [2 ]
Bezstarosti, Karel [2 ]
Bouzid, Rachid [1 ,5 ]
Klarenaar, Kim [1 ,6 ]
Jansen, Diahann T. S. L. [1 ,7 ]
Luijten, Robbie J. [1 ]
Demmers, Jeroen A. A. [2 ]
Buschow, Sonja I. [1 ]
机构
[1] Univ Med Ctr Rotterdam, Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands
[2] Univ Med Ctr Rotterdam, Erasmus MC, Prote Ctr, Dept Biochem, Rotterdam, Netherlands
[3] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote, Utrecht, Netherlands
[4] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands
[5] Merus NV, Utrecht, Netherlands
[6] UMC Utrecht, Div Labs Pharm & Biomed Genet, Utrecht, Netherlands
[7] Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands
关键词
ANTIGEN PRESENTATION; IDENTIFICATION; DECONVOLUTION; EXPRESSION; RESPONSES; EPITOPES; LEAD;
D O I
10.1038/s41541-025-01069-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 (R)) 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.
引用
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页数:13
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