The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides.
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, acyla...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5951580?pdf=render |
| _version_ | 1828835420122644480 |
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| author | Heidi S Schultz Søren Østergaard John Sidney Kasper Lamberth Alessandro Sette |
| author_facet | Heidi S Schultz Søren Østergaard John Sidney Kasper Lamberth Alessandro Sette |
| author_sort | Heidi S Schultz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T18:02:32Z |
| format | Article |
| id | doaj.art-a8f131360f08494690fb6dcbac90fd99 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T18:02:32Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a8f131360f08494690fb6dcbac90fd992022-12-22T00:16:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01135e019740710.1371/journal.pone.0197407The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides.Heidi S SchultzSøren ØstergaardJohn SidneyKasper LamberthAlessandro SetteImmunogenicity 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.http://europepmc.org/articles/PMC5951580?pdf=render |
| spellingShingle | Heidi S Schultz Søren Østergaard John Sidney Kasper Lamberth Alessandro Sette The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides. PLoS ONE |
| title | The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides. |
| title_full | The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides. |
| title_fullStr | The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides. |
| title_full_unstemmed | The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides. |
| title_short | The effect of acylation with fatty acids and other modifications on HLA class II:peptide binding and T cell stimulation for three model peptides. |
| title_sort | effect of acylation with fatty acids and other modifications on hla class ii peptide binding and t cell stimulation for three model peptides |
| url | http://europepmc.org/articles/PMC5951580?pdf=render |
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