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Crystal structure of the giant panda MHC class I complex: First insights into the viral peptide presentation profile in the bear family
Author(s) -
Yuan Hongyu,
Ma Lizhen,
Zhang Lijie,
Li Xiaoying,
Xia Chun
Publication year - 2020
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3980
Subject(s) - ctl* , biology , epitope , mhc class i , mhc restriction , major histocompatibility complex , t cell receptor , antigen presentation , cd8 , virology , cytotoxic t cell , microbiology and biotechnology , t cell , antigen , immune system , genetics , in vitro
The viral cytotoxic T lymphocyte (CTL) epitope peptides presented by classical MHC‐I molecules require the assembly of a peptide‐MHC‐I‐ β 2m (pMHC‐I) trimolecular complex for T cell receptor (TCR) recognition, which is the critical activation link for triggering antiviral T cell immunity. Research on T cell immunology in the Ursidae family, especially structural immunology, is still lacking. In this study, the structure of the key trimolecular complex pMHC‐I, which binds a peptide from canine distemper virus, was solved for the first time using giant panda as a representative species of Ursidae. The structural characteristics of the giant panda pMHC‐I complex (pAime‐128), including the unique pockets in the peptide‐binding groove (PBG), were analyzed in detail. Comparing the pAime‐128 to others in the bear family and extending the comparison to other mammals revealed distinct features. The interaction between MHC‐I and β 2m, the features of pAime‐128 involved in TCR docking and cluster of differentiation 8 (CD8) binding, the anchor sites in the PBG, and the CTL epitopes of potential viruses that infect pandas were clarified. Unique features of pMHC‐I viral antigen presentation in the panda were revealed by solving the three‐dimensional (3D) structure of pAime‐128. The distinct characteristics of pAime‐128 indicate an unusual event that emerged during the evolution of the MHC system in the bear family. These results provide a new platform for research on panda CTL immunity and the design of vaccines for application in the bear family.