Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity
IntroductionPsoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vβ13S1 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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1374581/full |
| _version_ | 1797268710211190784 |
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| author | Tatsushi Ishimoto Yukiyasu Arakawa Secil Vural Julia Stöhr Sigrid Vollmer Adrian Galinski Katherina Siewert Geraldine Rühl Yuri Poluektov Marc Delcommenne Orsolya Horvath Mengwen He Burkhard Summer Ralf Pohl Rehab Alharbi Klaus Dornmair Akiko Arakawa Jörg C. Prinz |
| author_facet | Tatsushi Ishimoto Yukiyasu Arakawa Secil Vural Julia Stöhr Sigrid Vollmer Adrian Galinski Katherina Siewert Geraldine Rühl Yuri Poluektov Marc Delcommenne Orsolya Horvath Mengwen He Burkhard Summer Ralf Pohl Rehab Alharbi Klaus Dornmair Akiko Arakawa Jörg C. Prinz |
| author_sort | Tatsushi Ishimoto |
| collection | DOAJ |
| description | IntroductionPsoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vβ13S1 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.MethodsWe screened databases with the peptide recognition motif of the Vα3S1/Vβ13S1 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.ResultsWe identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the Vα3S1/Vβ13S1 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.DiscussionOur 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. |
| first_indexed | 2024-04-25T01:36:48Z |
| format | Article |
| id | doaj.art-9d40d63e9367413db27f9f40a57c9739 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-25T01:36:48Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9d40d63e9367413db27f9f40a57c97392024-03-08T09:26:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13745811374581Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificityTatsushi Ishimoto0Yukiyasu Arakawa1Secil Vural2Julia Stöhr3Sigrid Vollmer4Adrian Galinski5Katherina Siewert6Geraldine Rühl7Yuri Poluektov8Marc Delcommenne9Orsolya Horvath10Mengwen He11Burkhard Summer12Ralf Pohl13Rehab Alharbi14Klaus Dornmair15Akiko Arakawa16Jörg C. Prinz17Department of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyInstitute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyInstitute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyMBL International, Woburn, MA, United StatesMBL International, Woburn, MA, United StatesDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyInstitute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyDepartment of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University Munich, Munich, GermanyIntroductionPsoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vβ13S1 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.MethodsWe screened databases with the peptide recognition motif of the Vα3S1/Vβ13S1 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.ResultsWe identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the Vα3S1/Vβ13S1 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.DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1374581/fullpsoriasispathogenic T-cell receptorT-cell receptor polyspecificityautoimmune responseenvironmental antigensdiseases triggers |
| spellingShingle | Tatsushi Ishimoto Yukiyasu Arakawa Secil Vural Julia Stöhr Sigrid Vollmer Adrian Galinski Katherina Siewert Geraldine Rühl Yuri Poluektov Marc Delcommenne Orsolya Horvath Mengwen He Burkhard Summer Ralf Pohl Rehab Alharbi Klaus Dornmair Akiko Arakawa Jörg C. Prinz Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity Frontiers in Immunology psoriasis pathogenic T-cell receptor T-cell receptor polyspecificity autoimmune response environmental antigens diseases triggers |
| title | Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity |
| title_full | Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity |
| title_fullStr | Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity |
| title_full_unstemmed | Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity |
| title_short | Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity |
| title_sort | multiple environmental antigens may trigger autoimmunity in psoriasis through t cell receptor polyspecificity |
| topic | psoriasis pathogenic T-cell receptor T-cell receptor polyspecificity autoimmune response environmental antigens diseases triggers |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1374581/full |
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