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

作者：Yanan Wu, Nianzhi Zhang, Keiichiro Hashimoto, Chun Xia, Johannes M. Dijkstra · 发表于：Frontiers in Immunology · 年份：2021 · DOI：10.3389/fimmu.2021.621153 · 被引用次数：35 · 研究领域：vaccines and immunoinformatics approaches、T-cell and B-cell Immunology、Immune Cell Function and Interaction

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 β 2 -microglobulin (β 2 -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 β 2 -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 β 2 -m hydrophobic knob into the peptide binding domain β-sheet floor. A comparison between divergent species indicates better sequence conservation of p...