A Glimpse of the Peptide Profile Presentation by Xenopus laevis MHC Class I: Crystal structure of PxeLA-UAA reveals a distinct peptide-binding groove

Lizhen Ma, Nianzhi Zhang, Zehui Qu, Ruiying Liang, Lijie Zhang, Bing Zhang, Geng Meng, Johannes M. Dijkstra, Shen Li, Max Chun Xia

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The African clawed frog, Xenopus laevis, is a model species for amphibians. Before metamorphosis, tadpoles do not efficiently express the single classical MHC class I (MHC-I) molecule Xela-UAA, but after metamorphosis, adults express this molecule in abundance. To elucidate the Ag-presenting mechanism of Xela-UAA, in this study, the Xela-UAA structure complex (pXela-UAAg) bound with a peptide from a synthetic random peptide library was determined. The amino acid homology between the Xela-UAA and MHC-I sequences of different species is <45%, and these differences are fully reflected in the three-dimensional structure of pXela-UAAg. Because of polymorphisms and interspecific differences in amino acid sequences, pXela-UAAg forms a distinct peptide-binding groove and presents a unique peptide profile. The most important feature of pXela-UAAg is the two–amino acid insertion in the a2-helical region, which forms a protrusion of ∼3.8 Å that is involved in TCR docking. Comparison of peptide–MHC-I complex (pMHC-I) structures showed that only four amino acids in b2-microglobulin that were bound to MHC-I are conserved in almost all jawed vertebrates, and the most unique feature in nonmammalian pMHC-I molecules is that the AB loop bound b2-microglobulin. Additionally, the binding distance between pMHC-I and CD8 molecules in nonmammals is different from that in mammals. These unique features of pXela-UAAg provide enhanced knowledge of T cell immunity and bridge the knowledge gap regarding the coevolutionary progression of the MHC-I complex from aquatic to terrestrial species. The Journal of Immunology, 2020, 204: 147–158.

Original languageEnglish
JournalJournal of Immunology
Issue number1
Publication statusPublished - 01-01-2020


All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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