Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis.
Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers load...
| Những tác giả chính: | , , , , , , , , |
|---|---|
| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
2004
|
| _version_ | 1826270122645389312 |
|---|---|
| author | Appel, H Kuon, W Kuhne, M Wu, P Kuhlmann, S Kollnberger, S Thiel, A Bowness, P Sieper, J |
| author_facet | Appel, H Kuon, W Kuhne, M Wu, P Kuhlmann, S Kollnberger, S Thiel, A Bowness, P Sieper, J |
| author_sort | Appel, H |
| collection | OXFORD |
| description | Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein-Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8+ T cells. The application of HLA-B27 tetramers in HLA-B27-related diseases was performed with nine recently described Chlamydia-derived peptides in synovial fluid and peripheral blood, to examine the CD8+ T cell response against Chlamydia trachomatis antigens in nine patients with Chlamydia-triggered reactive arthritis (Ct-ReA). Four of six HLA-B27+ Ct-ReA patients had specific synovial T cell binding to at least one HLA-B27/Chlamydia peptide tetramer. The HLA-B27/Chlamydia peptide 195 tetramer bound to synovial T cells from three of six patients and HLA-B27/Chlamydia peptide 133 tetramer to synovial T cells from two patients. However, the frequency of these cells was low (0.02-0.09%). Moreover, we demonstrate two methods to generate HLA-B27-restricted T cell lines. First, HLA-B27 tetramers and magnetic beads were used to sort antigen-specific CD8+ T cells. Second, Chlamydia-infected dendritic cells were used to stimulate CD8+ T cells ex vivo. Highly pure CD8 T cell lines could be generated ex vivo by magnetic sorting by using HLA-B27 tetramers loaded with an EBV peptide. The frequency of Chlamydia-specific, HLA-B27 tetramer-binding CD8+ T cells could be increased by stimulating CD8+ T cells ex vivo with Chlamydia-infected dendritic cells. We conclude that HLA-B27 tetramers are a useful tool for the detection and expansion of HLA-B27-restricted CD8+ T cells. T cells specific for one or more of three Chlamydia-derived peptides were found at low frequency in synovial fluid from HLA-B27+ patients with Ct-ReA. These cells can be expanded ex vivo, suggesting that they are immunologically functional. |
| first_indexed | 2024-03-06T21:35:54Z |
| format | Journal article |
| id | oxford-uuid:46439a7c-1c82-43ed-93cf-5fe627288ffb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:35:54Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:46439a7c-1c82-43ed-93cf-5fe627288ffb2022-03-26T15:12:39ZUse of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:46439a7c-1c82-43ed-93cf-5fe627288ffbEnglishSymplectic Elements at Oxford2004Appel, HKuon, WKuhne, MWu, PKuhlmann, SKollnberger, SThiel, ABowness, PSieper, JReports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein-Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8+ T cells. The application of HLA-B27 tetramers in HLA-B27-related diseases was performed with nine recently described Chlamydia-derived peptides in synovial fluid and peripheral blood, to examine the CD8+ T cell response against Chlamydia trachomatis antigens in nine patients with Chlamydia-triggered reactive arthritis (Ct-ReA). Four of six HLA-B27+ Ct-ReA patients had specific synovial T cell binding to at least one HLA-B27/Chlamydia peptide tetramer. The HLA-B27/Chlamydia peptide 195 tetramer bound to synovial T cells from three of six patients and HLA-B27/Chlamydia peptide 133 tetramer to synovial T cells from two patients. However, the frequency of these cells was low (0.02-0.09%). Moreover, we demonstrate two methods to generate HLA-B27-restricted T cell lines. First, HLA-B27 tetramers and magnetic beads were used to sort antigen-specific CD8+ T cells. Second, Chlamydia-infected dendritic cells were used to stimulate CD8+ T cells ex vivo. Highly pure CD8 T cell lines could be generated ex vivo by magnetic sorting by using HLA-B27 tetramers loaded with an EBV peptide. The frequency of Chlamydia-specific, HLA-B27 tetramer-binding CD8+ T cells could be increased by stimulating CD8+ T cells ex vivo with Chlamydia-infected dendritic cells. We conclude that HLA-B27 tetramers are a useful tool for the detection and expansion of HLA-B27-restricted CD8+ T cells. T cells specific for one or more of three Chlamydia-derived peptides were found at low frequency in synovial fluid from HLA-B27+ patients with Ct-ReA. These cells can be expanded ex vivo, suggesting that they are immunologically functional. |
| spellingShingle | Appel, H Kuon, W Kuhne, M Wu, P Kuhlmann, S Kollnberger, S Thiel, A Bowness, P Sieper, J Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. |
| title | Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. |
| title_full | Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. |
| title_fullStr | Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. |
| title_full_unstemmed | Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. |
| title_short | Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. |
| title_sort | use of hla b27 tetramers to identify low frequency antigen specific t cells in chlamydia triggered reactive arthritis |
| work_keys_str_mv | AT appelh useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT kuonw useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT kuhnem useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT wup useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT kuhlmanns useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT kollnbergers useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT thiela useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT bownessp useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis AT sieperj useofhlab27tetramerstoidentifylowfrequencyantigenspecifictcellsinchlamydiatriggeredreactivearthritis |