| First Author | Liu WJ | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 2 | Pages | 873-882 |
| PubMed ID | 27903740 | Mgi Jnum | J:291594 |
| Mgi Id | MGI:5927301 | Doi | 10.4049/jimmunol.1601542 |
| Citation | Liu WJ, et al. (2017) Protective T Cell Responses Featured by Concordant Recognition of Middle East Respiratory Syndrome Coronavirus-Derived CD8+ T Cell Epitopes and Host MHC. J Immunol 198(2):873-882 |
| abstractText | 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 alpha1 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. |
