The show and tell of cross-presentation

Blander, J. Magarian; Yee Mon, Kristel Joy; Jha, Atimukta; Roycroft, Dylan

doi:10.1016/bs.ai.2023.08.002

Cited by 1 publication

(1 citation statement)

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“…Possibly the NetMHCpan4.1 algorithm, trained on HLA-I peptides derived from mostly parenchymal (cancer) cells rather than DCs 36 , can less accurately predict binding of cross-presented peptides because DCs have a more complex antigen processing machinery. Whereas in parenchymal cells the generation of endogenous HLA-I peptides is (immuno)proteasome-driven, the generation of exogenous peptides for cross-presentation by DCs is a combined action of the (immuno)proteasome as well as endosomal proteases with very different cleavage specificities [60][61][62] . This is exemplified by the identification of SLP-derived peptides HLYSHPIIL (Pol 502-510 ) and HLYSHPIILG (Pol 502-511 ).…”

Section: Discussionmentioning

confidence: 99%

HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design

Buschow,

Kessler,

Doff

et al. 2024

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%