Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck
Under physiological conditions, CD8+ T cells need to recognize low numbers of antigenic pMHC class I complexes in the presence of a surplus of non-stimulatory, self pMHC class I on the surface of the APC. Non-stimulatory pMHC have been shown to enhance CD8+ T cell responses to low amounts of antigen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.721722/full |
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| author | Xiang Zhao Xiang Zhao Liang-Zhe Wu Liang-Zhe Wu Esther K. Y. Ng Esther K. Y. Ng Kerisa W. S. Leow Qianru Wei Qianru Wei Nicholas R. J. Gascoigne Nicholas R. J. Gascoigne Joanna Brzostek Joanna Brzostek |
| author_facet | Xiang Zhao Xiang Zhao Liang-Zhe Wu Liang-Zhe Wu Esther K. Y. Ng Esther K. Y. Ng Kerisa W. S. Leow Qianru Wei Qianru Wei Nicholas R. J. Gascoigne Nicholas R. J. Gascoigne Joanna Brzostek Joanna Brzostek |
| author_sort | Xiang Zhao |
| collection | DOAJ |
| description | Under physiological conditions, CD8+ T cells need to recognize low numbers of antigenic pMHC class I complexes in the presence of a surplus of non-stimulatory, self pMHC class I on the surface of the APC. Non-stimulatory pMHC have been shown to enhance CD8+ T cell responses to low amounts of antigenic pMHC, in a phenomenon called co-agonism, but the physiological significance and molecular mechanism of this phenomenon are still poorly understood. Our data show that co-agonist pMHC class I complexes recruit CD8-bound Lck to the immune synapse to modulate CD8+ T cell signaling pathways, resulting in enhanced CD8+ T cell effector functions and proliferation, both in vitro and in vivo. Moreover, co-agonism can boost T cell proliferation through an extrinsic mechanism, with co-agonism primed CD8+ T cells enhancing Akt pathway activation and proliferation in neighboring CD8+ T cells primed with low amounts of antigen. |
| first_indexed | 2024-12-20T00:20:02Z |
| format | Article |
| id | doaj.art-77356d9f19ec4a2eb49a0714187b27e7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T00:20:02Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-77356d9f19ec4a2eb49a0714187b27e72022-12-21T20:00:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.721722721722Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound LckXiang Zhao0Xiang Zhao1Liang-Zhe Wu2Liang-Zhe Wu3Esther K. Y. Ng4Esther K. Y. Ng5Kerisa W. S. Leow6Qianru Wei7Qianru Wei8Nicholas R. J. Gascoigne9Nicholas R. J. Gascoigne10Joanna Brzostek11Joanna Brzostek12Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeImmunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeImmunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeImmunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeImmunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeImmunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeUnder physiological conditions, CD8+ T cells need to recognize low numbers of antigenic pMHC class I complexes in the presence of a surplus of non-stimulatory, self pMHC class I on the surface of the APC. Non-stimulatory pMHC have been shown to enhance CD8+ T cell responses to low amounts of antigenic pMHC, in a phenomenon called co-agonism, but the physiological significance and molecular mechanism of this phenomenon are still poorly understood. Our data show that co-agonist pMHC class I complexes recruit CD8-bound Lck to the immune synapse to modulate CD8+ T cell signaling pathways, resulting in enhanced CD8+ T cell effector functions and proliferation, both in vitro and in vivo. Moreover, co-agonism can boost T cell proliferation through an extrinsic mechanism, with co-agonism primed CD8+ T cells enhancing Akt pathway activation and proliferation in neighboring CD8+ T cells primed with low amounts of antigen.https://www.frontiersin.org/articles/10.3389/fimmu.2021.721722/fullco-agonismLckT cell receptornon-stimulatory peptide MHCT cell signalingT cell effector functions |
| spellingShingle | Xiang Zhao Xiang Zhao Liang-Zhe Wu Liang-Zhe Wu Esther K. Y. Ng Esther K. Y. Ng Kerisa W. S. Leow Qianru Wei Qianru Wei Nicholas R. J. Gascoigne Nicholas R. J. Gascoigne Joanna Brzostek Joanna Brzostek Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck Frontiers in Immunology co-agonism Lck T cell receptor non-stimulatory peptide MHC T cell signaling T cell effector functions |
| title | Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck |
| title_full | Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck |
| title_fullStr | Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck |
| title_full_unstemmed | Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck |
| title_short | Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck |
| title_sort | non stimulatory pmhc enhance cd8 t cell effector functions by recruiting coreceptor bound lck |
| topic | co-agonism Lck T cell receptor non-stimulatory peptide MHC T cell signaling T cell effector functions |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.721722/full |
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