Journal
JOURNAL OF IMMUNOLOGY
Volume 198, Issue 2, Pages 873-882Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1601542
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Funding
- China Ministry of Science and Technology National 973 Project [2015CB910500]
- National Key Plan for Scientific Research and Development of China [2016YFD0500301, 2016YFD0500304, 2016YFD0500305]
- National Natural Science Foundation of China [81373141, 81401312, 81461168030]
- Municipal Healthcare Joint Innovation Major Project of Guangzhou [201604020011]
- Megaproject for Infectious Disease Research of China [2016ZX10004222-003, 2014ZX10004001-002, 2014ZX10004001-006, 2012ZX10004501-004]
- Thousand Talents Plan Award of China
- National Natural Science Foundation of China Innovative Research Group [81321063]
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The coordinated recognition of virus-derived T cell epitopes andMHCmolecules 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 Trp(73) on the alpha 1 helix of murine MHC I H-2K(d). 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.
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