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, Johannes M. Dijkstra, Xiaoying Li, Zhenbao Wang, Junya Wang, Yanan Wu, Chun Xia

Research output: Contribution to journalArticlepeer-review

13 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

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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