ArticlePloS one2018
The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 30 citations in OpenAlex.
- Development of Zalfermin, a Long-Acting Proteolytically Stabilized FGF21 Analog.Journal of medicinal chemistry · 2024Article
- Site-selective fatty acid chain conjugation of the N-terminus of the recombinant human granulocyte colony-stimulating factor.Frontiers in bioengineering and biotechnology · 2024Article
- Preparation and Characterization of Site-Specific Fatty Chain-Modified Recombinant Human Granulocyte Colony Stimulating Factor.Frontiers in bioengineering and biotechnology · 2022Article
- Acylation, a Conductor of Ghrelin Function in Brain Health and Disease.Frontiers in physiology · 2022Review
- Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta: a GWAS.BMC medicine · 2020Article
- Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics.Amino acids · 2020Review
- Evaluation of T-activated proteins as recall antigens to monitor Epstein-Barr virus and human cytomegalovirus-specific T cells in a clinical trial setting.Journal of translational medicine · 2020Article
- Influence of Production Process and Scale on Quality of Polypeptide Drugs: a Case Study on GLP-1 Analogs.Pharmaceutical research · 2020Article
- A review of lipidation in the development of advanced protein and peptide therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2019Review
- Novel enzyme-resistant pancreatic polypeptide analogs evoke pancreatic beta-cell rest, enhance islet cell turnover, and inhibit food intake in mice.BioFactors (Oxford, England)Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunogenicity is a major concern in drug development as anti-drug antibodies in many cases affect both patient safety and drug efficacy. Another concern is often the limited half-life of drugs, which can be altered by different chemical modifications, like acylation with fatty acids. However, acylation with fatty acids has been shown in some cases to modulate T cell activation. Therefore, to understand the role of acylation with fatty acids on immunogenicity we tested three immunogenic non-acylated peptides and 14 of their acylated analogues for binding to 26 common HLA class II alleles, and their ability to activate T cells in an ex vivo T cell assay. Changes in binding affinity associated with acylation with fatty acids were typically modest, though a significant decrease was observed for influenza HA acylated with a stearic acid, and affinities for DQ alleles were consistently increased. Importantly, we showed that for all three immunogenic peptides acylation with fatty acids decreased their capacity to activate T cells, a trend particularly evident with longer fatty acids typically positioned within the peptide HLA class II binding core region, or when closer to the C-terminus. With these results we have demonstrated that acylation with fatty acids of immunogenic peptides can lower their stimulatory capacity, which could be important knowledge for drug design and immunogenicity mitigation.
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