Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First

Yanan Wu, Nianzhi Zhang, Keiichiro Hashimoto, Chun Xia, Johannes M. Dijkstra

研究成果: ジャーナルへの寄稿学術論文査読

16 被引用数 (Scopus)


Structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar. However, whereas pMHC-II complexes include similar-sized IIα and IIβ chains, pMHC-I complexes include a heavy chain (HC) and a single domain molecule β2-microglobulin (β2-m). Recently, we elucidated several pMHC-I and pMHC-II structures of primitive vertebrate species. In the present study, a comprehensive comparison of pMHC-I and pMHC-II structures helps to understand pMHC structural evolution and supports the earlier proposed—though debated—direction of MHC evolution from class II-type to class I. Extant pMHC-II structures share major functional characteristics with a deduced MHC-II-type homodimer ancestor. Evolutionary establishment of pMHC-I presumably involved important new functions such as (i) increased peptide selectivity by binding the peptides in a closed groove (ii), structural amplification of peptide ligand sequence differences by binding in a non-relaxed fashion, and (iii) increased peptide selectivity by syngeneic heterotrimer complex formation between peptide, HC, and β2-m. These new functions were associated with structures that since their establishment in early pMHC-I have been very well conserved, including a shifted and reorganized P1 pocket (aka A pocket), and insertion of a β2-m hydrophobic knob into the peptide binding domain β-sheet floor. A comparison between divergent species indicates better sequence conservation of peptide binding domains among MHC-I than among MHC-II, agreeing with more demanding interactions within pMHC-I complexes. In lungfishes, genes encoding fusions of all MHC-IIα and MHC-IIβ extracellular domains were identified, and although these lungfish genes presumably derived from classical MHC-II, they provide an alternative mechanistic hypothesis for how evolution from class II-type to class I may have occurred.

ジャーナルFrontiers in Immunology
出版ステータス出版済み - 14-06-2021

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学


「Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。