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Article: Polymeric structure and host toll-like receptor 4 dictate immunogenicity of NY-ESO-1 antigen in vivo

TitlePolymeric structure and host toll-like receptor 4 dictate immunogenicity of NY-ESO-1 antigen in vivo
Authors
Issue Date2011
Citation
Journal of Biological Chemistry, 2011, v. 286, n. 43, p. 37077-37084 How to Cite?
AbstractIn search of intrinsic factors that contribute to the distinctively strong immunogenicity of a non-mutated cancer/testis antigen, we found that NY-ESO-1 forms polymeric structures through disulfide bonds. NY-ESO-1 binding to immature dendritic cells was dependent on its polymeric structure and involved Toll-like receptor-4 (TLR4) on the surface of immature dendritic cells in mouse and human. Gene gun-delivered plasmid encoding the wild-type NY-ESO-1 readily induced T cell-dependent antibody (Ab) responses in wild-type C57BL/10 mice but not TLR4-knock-out C57BL/10ScNJ mice. Disrupting polymeric structures of NY-ESO-1 by cysteine-to-serine (Cys-to-Ser) substitutions lead to diminished immunogenicity and altered TLR4-dependence in the induced Ab response. To demonstrate its adjuvant effect, NY-ESO-1 was fused with a major mugwort pollen allergen Art v 1 and a tumor-associated antigen, carbonic anhydrase 9. Plasmid DNA vaccines encoding the fusion genes generated robust immune responses against otherwise non-immunogenic targets in mice. Polymeric structure and TLR4 may play important roles in rendering NY-ESO-1 immunogenic and thus serve as a potent molecular adjuvant. NY-ESO-1 thus represents the first example of a cancer/testis antigen that is a also damage-associated molecular pattern.
Persistent Identifierhttp://hdl.handle.net/10722/285684
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yanan-
dc.contributor.authorTian, Xiaoli-
dc.contributor.authorLeitner, Wolfgang W.-
dc.contributor.authorAldridge, Michael E.-
dc.contributor.authorZheng, Junying-
dc.contributor.authorYu, Zhiya-
dc.contributor.authorRestifo, Nicholas P.-
dc.contributor.authorWeiss, Richard-
dc.contributor.authorScheiblhofer, Sandra-
dc.contributor.authorXie, Chong-
dc.contributor.authorSun, Ren-
dc.contributor.authorCheng, Genhong-
dc.contributor.authorZeng, Gang-
dc.date.accessioned2020-08-18T04:56:22Z-
dc.date.available2020-08-18T04:56:22Z-
dc.date.issued2011-
dc.identifier.citationJournal of Biological Chemistry, 2011, v. 286, n. 43, p. 37077-37084-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/285684-
dc.description.abstractIn search of intrinsic factors that contribute to the distinctively strong immunogenicity of a non-mutated cancer/testis antigen, we found that NY-ESO-1 forms polymeric structures through disulfide bonds. NY-ESO-1 binding to immature dendritic cells was dependent on its polymeric structure and involved Toll-like receptor-4 (TLR4) on the surface of immature dendritic cells in mouse and human. Gene gun-delivered plasmid encoding the wild-type NY-ESO-1 readily induced T cell-dependent antibody (Ab) responses in wild-type C57BL/10 mice but not TLR4-knock-out C57BL/10ScNJ mice. Disrupting polymeric structures of NY-ESO-1 by cysteine-to-serine (Cys-to-Ser) substitutions lead to diminished immunogenicity and altered TLR4-dependence in the induced Ab response. To demonstrate its adjuvant effect, NY-ESO-1 was fused with a major mugwort pollen allergen Art v 1 and a tumor-associated antigen, carbonic anhydrase 9. Plasmid DNA vaccines encoding the fusion genes generated robust immune responses against otherwise non-immunogenic targets in mice. Polymeric structure and TLR4 may play important roles in rendering NY-ESO-1 immunogenic and thus serve as a potent molecular adjuvant. NY-ESO-1 thus represents the first example of a cancer/testis antigen that is a also damage-associated molecular pattern.-
dc.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.titlePolymeric structure and host toll-like receptor 4 dictate immunogenicity of NY-ESO-1 antigen in vivo-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M111.280123-
dc.identifier.pmid21900253-
dc.identifier.pmcidPMC3199455-
dc.identifier.scopuseid_2-s2.0-80054816396-
dc.identifier.volume286-
dc.identifier.issue43-
dc.identifier.spage37077-
dc.identifier.epage37084-
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000296542400008-
dc.identifier.issnl0021-9258-

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