5GSR

Mouse MHC class I H-2Kd with a MERS-CoV-derived peptide I5A

Summary for 5GSR

• Entry DOI: 10.2210/pdb5gsr/pdb
• Related: 5GSV 5GSX
• Descriptor: Beta-2-microglobulin, H-2 class I histocompatibility antigen, K-D alpha chain, 9-mer peptide from Spike protein, ... (4 entities in total)
• Functional Keywords: mouse, h-2kd, mers-cov, t-cell, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted . Note=(Microbial infection) In the presence of M: P61769; Membrane; Single-pass type I membrane protein: P01902
• Total number of polymer chains: 6
• Total formula weight: 89711.84

Authors

Liu, K.,Chai, Y.,Qi, J.,Tan, W.,Liu, W.J.,Gao, G.F. (deposition date: 2016-08-17, release date: 2017-04-26, Last modification date: 2024-10-16)

Primary citation

Liu, W.J.,Lan, J.,Liu, K.,Deng, Y.,Yao, Y.,Wu, S.,Chen, H.,Bao, L.,Zhang, H.,Zhao, M.,Wang, Q.,Han, L.,Chai, Y.,Qi, J.,Zhao, J.,Meng, S.,Qin, C.,Gao, G.F.,Tan, W.
Protective T Cell Responses Featured by Concordant Recognition of Middle East Respiratory Syndrome Coronavirus-Derived CD8+ T Cell Epitopes and Host MHC.
J. Immunol., 198:873-882, 2017

PubMed Abstract: 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 Trp on the α1 helix of murine MHC I H-2K 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.

PubMed: 27903740
DOI: 10.4049/jimmunol.1601542

Experimental method

X-RAY DIFFRACTION (2.198 Å)