Protective T Cell Responses Featured by Concordant Recognition of Middle East Respiratory Syndrome Coronavirus–Derived CD8+ T Cell Epitopes and Host MHC
| العنوان: | Protective T Cell Responses Featured by Concordant Recognition of Middle East Respiratory Syndrome Coronavirus–Derived CD8+ T Cell Epitopes and Host MHC |
|---|---|
| المؤلفون: | Kefang Liu, William J. Liu, Qihui Wang, Min Zhao, Chuan Qin, Haifeng Zhang, Jincun Zhao, Hong Chen, Ling-xia Han, Jiaming Lan, Lingling Bao, Shaolian Wu, Yao Deng, Jianxun Qi, Songdong Meng, Yanfeng Yao, George F. Gao, Wenjie Tan, Yan Chai |
| المصدر: | The Journal of Immunology. 198:873-882 |
| بيانات النشر: | The American Association of Immunologists, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Enzyme-Linked Immunospot Assay, T cell, Immunology, Epitopes, T-Lymphocyte, CD8-Positive T-Lymphocytes, Biology, Crystallography, X-Ray, Lymphocyte Activation, Major histocompatibility complex, Epitope, Mice, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Immune system, MHC class I, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, Histocompatibility Antigen H-2D, Antigen Presentation, Mice, Inbred BALB C, Circular Dichroism, Viral Vaccines, MHC restriction, Virology, Molecular biology, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Middle East Respiratory Syndrome Coronavirus, biology.protein, Female, Coronavirus Infections, CD8, 030215 immunology |
| الوصف: | The coordinated recognition of virus-derived T cell epitopes and MHC molecules by T cells plays a pivotal role in cellular immunity–mediated virus clearance. It has been demonstrated that the conformation of MHC class I (MHC I) molecules can be adjusted by the presented peptide, which impacts T cell activation. However, it is still largely unknown whether the conformational shift of MHC I influences the protective effect of virus-specific T cells. In this study, utilizing the Middle East respiratory syndrome coronavirus–infected mouse model, we observed that through the unusual secondary anchor Ile5, a CD8+ T cell epitope drove the conformational fit of Trp73 on the α1 helix of murine MHC I H-2Kd. In vitro renaturation and circular dichroism assays indicated that this shift of the structure did not influence the peptide/MHC I binding affinity. Nevertheless, the T cell recognition and the protective effect of the peptide diminished when we made an Ile to Ala mutation at position 5 of the original peptide. The molecular bases of the concordant recognition of T cell epitopes and host MHC-dependent protection were demonstrated through both crystal structure determination and tetramer staining using the peptide–MHC complex. Our results indicate a coordinated MHC I/peptide interaction mechanism and provide a beneficial reference for T cell–oriented vaccine development against emerging viruses such as Middle East respiratory syndrome coronavirus. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e3e2b8d65867378e53813959c91f3a9Test https://doi.org/10.4049/jimmunol.1601542Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6e3e2b8d65867378e53813959c91f3a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
|---|