The structure of the MHC class i molecule of bony fishes provides insights into the conserved nature of the antigen-presenting system

Zhaosan Chen, Nianzhi Zhang, Jianxun Qi, Rong Chen, J・m Dijkstra, Xiaoying Li, Zhenbao Wang, Junya Wang, Yanan Wu, Chun Xia

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

MHC molecules evolved with the descent of jawed fishes some 350-400 million years ago. However, very little is known about the structural features of primitive MHC molecules. To gain insight into these features, we focused on the MHC class I Ctid-UAA of the evolutionarily distant grass carp (Ctenopharyngodon idella). The Ctid-UAA H chain and b2-microglobulin (Ctid-b2m) were refolded in vitro in the presence of peptides from viruses that infect carp. The resulting peptide-Ctid-UAA (p/Ctid-UAA) structures revealed the classical MHC class I topology with structural variations. In comparison with known mammalian and chicken peptide-MHC class I (p/MHC I) complexes, p/Ctid-UAA structure revealed several distinct features. Notably, 1) although the peptide ligand conventionally occupied all six pockets (A-F) of the Ag-binding site, the binding mode of the P3 side chain to pocket D was not observed in other p/MHC I structures; 2) the AB loop between b strands of the a1 domain of p/Ctid-UAA complex comes into contact with Ctid-b2m, an interaction observed only in chicken p/BF2∗2101-b2m complex; and 3) the CD loop of the a3 domain, which in mammals forms a contact with CD8, has a unique position in p/Ctid-UAA that does not superimpose with the structures of any known p/MHC I complexes, suggesting that the p/Ctid-UAA to Ctid-CD8 binding mode may be distinct. This demonstration of the structure of a bony fish MHC class I molecule provides a foundation for understanding the evolution of primitive class I molecules, how they present peptide Ags, and how they might control T cell responses.

Original languageEnglish
Pages (from-to)3668-3678
Number of pages11
JournalJournal of Immunology
Volume199
Issue number10
DOIs
Publication statusPublished - 15-11-2017

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Fishes
Antigens
Peptides
Carps
Chickens
Mammals
Binding Sites
Ligands
Viruses
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Chen, Zhaosan ; Zhang, Nianzhi ; Qi, Jianxun ; Chen, Rong ; Dijkstra, J・m ; Li, Xiaoying ; Wang, Zhenbao ; Wang, Junya ; Wu, Yanan ; Xia, Chun. / The structure of the MHC class i molecule of bony fishes provides insights into the conserved nature of the antigen-presenting system. In: Journal of Immunology. 2017 ; Vol. 199, No. 10. pp. 3668-3678.
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abstract = "MHC molecules evolved with the descent of jawed fishes some 350-400 million years ago. However, very little is known about the structural features of primitive MHC molecules. To gain insight into these features, we focused on the MHC class I Ctid-UAA of the evolutionarily distant grass carp (Ctenopharyngodon idella). The Ctid-UAA H chain and b2-microglobulin (Ctid-b2m) were refolded in vitro in the presence of peptides from viruses that infect carp. The resulting peptide-Ctid-UAA (p/Ctid-UAA) structures revealed the classical MHC class I topology with structural variations. In comparison with known mammalian and chicken peptide-MHC class I (p/MHC I) complexes, p/Ctid-UAA structure revealed several distinct features. Notably, 1) although the peptide ligand conventionally occupied all six pockets (A-F) of the Ag-binding site, the binding mode of the P3 side chain to pocket D was not observed in other p/MHC I structures; 2) the AB loop between b strands of the a1 domain of p/Ctid-UAA complex comes into contact with Ctid-b2m, an interaction observed only in chicken p/BF2∗2101-b2m complex; and 3) the CD loop of the a3 domain, which in mammals forms a contact with CD8, has a unique position in p/Ctid-UAA that does not superimpose with the structures of any known p/MHC I complexes, suggesting that the p/Ctid-UAA to Ctid-CD8 binding mode may be distinct. This demonstration of the structure of a bony fish MHC class I molecule provides a foundation for understanding the evolution of primitive class I molecules, how they present peptide Ags, and how they might control T cell responses.",
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The structure of the MHC class i molecule of bony fishes provides insights into the conserved nature of the antigen-presenting system. / Chen, Zhaosan; Zhang, Nianzhi; Qi, Jianxun; Chen, Rong; Dijkstra, J・m; Li, Xiaoying; Wang, Zhenbao; Wang, Junya; Wu, Yanan; Xia, Chun.

In: Journal of Immunology, Vol. 199, No. 10, 15.11.2017, p. 3668-3678.

Research output: Contribution to journalArticle

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