HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD
HLA-DR3 (DR3) is one of the dominant HLA-DR alleles associated with systemic lupus erythematosus (SLE) susceptibility. Our previous studies showed multiple intramolecular DR3 restricted T cell epitopes in the Smith D (SmD) protein, from which we generated a non-homologous, bacterial epitope mimics l...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.928374/full |
| _version_ | 1797991551948816384 |
|---|---|
| author | Zhenhuan Zhao Zhenhuan Zhao Ashley N. Anderson Carol C. Kannapell Carol C. Kannapell William W. Kwok Felicia Gaskin Shu Man Fu Shu Man Fu |
| author_facet | Zhenhuan Zhao Zhenhuan Zhao Ashley N. Anderson Carol C. Kannapell Carol C. Kannapell William W. Kwok Felicia Gaskin Shu Man Fu Shu Man Fu |
| author_sort | Zhenhuan Zhao |
| collection | DOAJ |
| description | HLA-DR3 (DR3) is one of the dominant HLA-DR alleles associated with systemic lupus erythematosus (SLE) susceptibility. Our previous studies showed multiple intramolecular DR3 restricted T cell epitopes in the Smith D (SmD) protein, from which we generated a non-homologous, bacterial epitope mimics library. From this library we identified ABC247-261 Mimic as one new DR3 restricted bacterial T cell epitope from the ABC transporter ATP-binding protein in Clostridium tetani. It activated and induced autoreactive SmD66-80-specific T cells and induced autoantibodies to lupus-related autoantigens in vivo. Compared to healthy donors, SLE patients have a greater percentage of cross-reactive T cells to ABC247-261 Mimic and SmD66-80. In addition, we analyzed the ability of single DR3 restricted Tetanus toxoid (TT) T cell epitopes to induce autoimmune T cells. We found that the immunodominant TT epitope TT826-845 stimulated SmD66-80 reactive T cells but failed to induce persistent anti-SmD autoantibodies compared to the ABC247-261 Mimic. Thus, exposure to the ABC247-261 Mimic epitope may contribute to autoimmunity in susceptible DR3 individuals. |
| first_indexed | 2024-04-11T08:54:06Z |
| format | Article |
| id | doaj.art-8a5387e845c1455892485b2493883d1b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T08:54:06Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8a5387e845c1455892485b2493883d1b2022-12-22T04:33:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.928374928374HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmDZhenhuan Zhao0Zhenhuan Zhao1Ashley N. Anderson2Carol C. Kannapell3Carol C. Kannapell4William W. Kwok5Felicia Gaskin6Shu Man Fu7Shu Man Fu8Division of Rheumatology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesCenter for Immunity, Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesCenter for Immunity, Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesDivision of Rheumatology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesCenter for Immunity, Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesBenaroya Research Institute, Virginia Mason, Seattle, WA, United StatesDepartment of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United StatesDivision of Rheumatology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesCenter for Immunity, Inflammation and Regenerative Medicine, Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, United StatesHLA-DR3 (DR3) is one of the dominant HLA-DR alleles associated with systemic lupus erythematosus (SLE) susceptibility. Our previous studies showed multiple intramolecular DR3 restricted T cell epitopes in the Smith D (SmD) protein, from which we generated a non-homologous, bacterial epitope mimics library. From this library we identified ABC247-261 Mimic as one new DR3 restricted bacterial T cell epitope from the ABC transporter ATP-binding protein in Clostridium tetani. It activated and induced autoreactive SmD66-80-specific T cells and induced autoantibodies to lupus-related autoantigens in vivo. Compared to healthy donors, SLE patients have a greater percentage of cross-reactive T cells to ABC247-261 Mimic and SmD66-80. In addition, we analyzed the ability of single DR3 restricted Tetanus toxoid (TT) T cell epitopes to induce autoimmune T cells. We found that the immunodominant TT epitope TT826-845 stimulated SmD66-80 reactive T cells but failed to induce persistent anti-SmD autoantibodies compared to the ABC247-261 Mimic. Thus, exposure to the ABC247-261 Mimic epitope may contribute to autoimmunity in susceptible DR3 individuals.https://www.frontiersin.org/articles/10.3389/fimmu.2022.928374/fullT cell epitopeHLA-DR3environmental bacteriamolecular mimicryautoantigenSmith D (SmD) |
| spellingShingle | Zhenhuan Zhao Zhenhuan Zhao Ashley N. Anderson Carol C. Kannapell Carol C. Kannapell William W. Kwok Felicia Gaskin Shu Man Fu Shu Man Fu HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD Frontiers in Immunology T cell epitope HLA-DR3 environmental bacteria molecular mimicry autoantigen Smith D (SmD) |
| title | HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD |
| title_full | HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD |
| title_fullStr | HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD |
| title_full_unstemmed | HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD |
| title_short | HLA-DR3 restricted environmental epitopes from the bacterium Clostridium tetani have T cell cross-reactivity to the SLE-related autoantigen SmD |
| title_sort | hla dr3 restricted environmental epitopes from the bacterium clostridium tetani have t cell cross reactivity to the sle related autoantigen smd |
| topic | T cell epitope HLA-DR3 environmental bacteria molecular mimicry autoantigen Smith D (SmD) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.928374/full |
| work_keys_str_mv | AT zhenhuanzhao hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT zhenhuanzhao hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT ashleynanderson hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT carolckannapell hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT carolckannapell hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT williamwkwok hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT feliciagaskin hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT shumanfu hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd AT shumanfu hladr3restrictedenvironmentalepitopesfromthebacteriumclostridiumtetanihavetcellcrossreactivitytotheslerelatedautoantigensmd |