Publication:
Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity

dc.contributor.coauthorIshimoto, Tatsushi
dc.contributor.coauthorArakawa, Yukiyasu
dc.contributor.coauthorStöhr, Julia
dc.contributor.coauthorVollmer, Sigrid
dc.contributor.coauthorGalinski, Adrian
dc.contributor.coauthorSiewert, Katherina
dc.contributor.coauthorRuehl, Geraldine
dc.contributor.coauthorPoluektov, Yuri
dc.contributor.coauthorDelcommenne, Marc
dc.contributor.coauthorHorvath, Orsolya
dc.contributor.coauthorHe, Mengwen
dc.contributor.coauthorSummer, Burkhard
dc.contributor.coauthorPohl, Ralf
dc.contributor.coauthorAlharbi, Rehab
dc.contributor.coauthorDornmair, Klaus
dc.contributor.coauthorArakawa, Akiko
dc.contributor.coauthorPrinz, Jörg C.
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorVural, Seçil
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-12-29T09:37:35Z
dc.date.issued2024
dc.description.abstractIntroduction: Psoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a V alpha 3S1/V beta 13S1 T-cell receptor (TCR) from a lesional psoriatic CD8(+) T-cell clone we had discovered that, as an underlying pathomechanism, HLA-C*06:02 mediates an autoimmune response against melanocytes in psoriasis, and we had identified an epitope from ADAMTS-like protein 5 (ADAMTSL5) as a melanocyte autoantigen. The conditions activating the psoriatic autoimmune response in genetically predisposed individuals throughout life remain incompletely understood. Here, we aimed to identify environmental antigens that might trigger autoimmunity in psoriasis because of TCR polyspecificity. Methods: We screened databases with the peptide recognition motif of the V alpha 3S1/V beta 13S1 TCR for environmental proteins containing peptides activating this TCR. We investigated the immunogenicity of these peptides for psoriasis patients and healthy controls by lymphocyte stimulation experiments and peptide-loaded HLA-C*06:02 tetramers. Results: We identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the V alpha 3S1/V beta 13S1 TCR and CD8(+) T cells from psoriasis patients. Using fluorescent HLA-C*06:02 tetramers loaded with ADAMTSL5 or wheat peptides, we find that the same CD8(+) T cells may recognize both autoantigen and environmental antigens. A wheat-free diet could alleviate psoriasis in several patients. Discussion: Our results show that due to TCR polyspecificity, several environmental antigens corresponding to previously suspected psoriasis risk conditions converge in the reactivity of a pathogenic psoriatic TCR and might thus be able to stimulate the psoriatic autoimmune response against melanocytes. Avoiding the corresponding environmental risk factors could contribute to the management of psoriasis.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.openaccessgold
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipThe author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The author(s) declare this work was supported by the German Research Foundation grants PR 241/5-1 and 5-2 (JP), the Japanese Dermatological Association Grant-In-Aid for Study Abroad (TI), the Japan Society for the Promotion of Science grant 21K16234 (YA), the TUBITAK 2219 postdoctoral research grant and L'OREAL UNESCO for Women in Science Fellowship of Turkey (SVu), the LMU-China Scholarship Council Program scholarship No. 201706160167 (MH), the Ministry of Health, Dammam, Saudi Arabia, educational grant (RA), and the German Federal Ministry of Education and Research, BMBF/VIP program, grant VIP0376 -03V0511 (KD, JP).
dc.description.volume15
dc.identifier.doi10.3389/fimmu.2024.1374581
dc.identifier.issn1664-3224
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85188240681
dc.identifier.urihttps://doi.org/10.3389/fimmu.2024.1374581
dc.identifier.urihttps://hdl.handle.net/20.500.14288/22401
dc.identifier.wos1189725700001
dc.keywordsPsoriasis
dc.keywordsPathogenic T-cell receptor
dc.keywordsT-cell receptor polyspecificity
dc.keywordsAutoimmune response
dc.keywordsEnvironmental antigens
dc.keywordsDiseases triggers
dc.keywordsHLA-C*06:02
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.grantnoGerman Research Foundation [PR 241/5-1, 5-2]
dc.relation.grantnoJapanese Dermatological Association
dc.relation.grantnoJapan Society for the Promotion of Science [21K16234]
dc.relation.grantnoTUBITAK [2219]
dc.relation.grantnoL'OREAL UNESCO for Women in Science Fellowship of Turkey
dc.relation.grantnoLMU-China Scholarship Council Program scholarship [201706160167]
dc.relation.grantnoMinistry of Health, Dammam, Saudi Arabia
dc.relation.grantnoGerman Federal Ministry of Education and Research, BMBF/VIP program [VIP0376 -03V0511]
dc.relation.ispartofFrontiers in Immunology
dc.subjectImmunology
dc.titleMultiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorVural, Seçil
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2School of Medicine
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relation.isOrgUnitOfPublication.latestForDiscoveryd02929e1-2a70-44f0-ae17-7819f587bedd
relation.isParentOrgUnitOfPublication17f2dc8e-6e54-4fa8-b5e0-d6415123a93e
relation.isParentOrgUnitOfPublication.latestForDiscovery17f2dc8e-6e54-4fa8-b5e0-d6415123a93e

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