T-cell receptor-HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis
| Autor: | Tatiana Sandalova, Remi-Andre Olsen, Kerstin M. Ahlgren, Jan Wahlström, Natalia V. Rivera, Marcus Ronninger, Max Käller, Sverker Lundin, Anders Eklund, M. Ostadkarampour, Britta Lötstedt, Lina Sylwan, Ylva Kaiser, Johan Grunewald, Adnane Achour, Francesco Vezzi |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Adult CD4-Positive T-Lymphocytes Male Models Molecular Receptor expression Receptors Antigen T-Cell Vimentin Human leukocyte antigen 03 medical and health sciences 0302 clinical medicine Antigen Sarcoidosis Pulmonary Bronchoscopy Medicine Humans Receptor Lung Sweden biology medicine.diagnostic_test business.industry T-cell receptor Middle Aged medicine.disease Flow Cytometry 030104 developmental biology Bronchoalveolar lavage 030228 respiratory system Immunology biology.protein Female Sarcoidosis business Bronchoalveolar Lavage Fluid HLA-DRB1 Chains |
| Zdroj: | The European respiratory journal. 47(3) |
| ISSN: | 1399-3003 |
| Popis: | In pulmonary sarcoidosis, CD4+ T-cells expressing T-cell receptor Vα2.3 accumulate in the lungs of HLA-DRB1*03+ patients. To investigate T-cell receptor-HLA-DRB1*03 interactions underlying recognition of hitherto unknown antigens, we performed detailed analyses of T-cell receptor expression on bronchoalveolar lavage fluid CD4+ T-cells from sarcoidosis patients.Pulmonary sarcoidosis patients (n=43) underwent bronchoscopy with bronchoalveolar lavage. T-cell receptor α and β chains of CD4+ T-cells were analysed by flow cytometry, DNA-sequenced, and three-dimensional molecular models of T-cell receptor-HLA-DRB1*03 complexes generated.Simultaneous expression of Vα2.3 with the Vβ22 chain was identified in the lungs of all HLA-DRB1*03+ patients. Accumulated Vα2.3/Vβ22-expressing T-cells were highly clonal, with identical or near-identical Vα2.3 chain sequences and inter-patient similarities in Vβ22 chain amino acid distribution. Molecular modelling revealed specific T-cell receptor-HLA-DRB1*03-peptide interactions, with a previously identified, sarcoidosis-associated vimentin peptide, (Vim)429–443 DSLPLVDTHSKRTLL, matching both the HLA peptide-binding cleft and distinct T-cell receptor features perfectly.We demonstrate, for the first time, the accumulation of large clonal populations of specific Vα2.3/Vβ22 T-cell receptor-expressing CD4+ T-cells in the lungs of HLA-DRB1*03+ sarcoidosis patients. Several distinct contact points between Vα2.3/Vβ22 receptors and HLA-DRB1*03 molecules suggest presentation of prototypic vimentin-derived peptides. |
| Databáze: | OpenAIRE |
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