Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
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)....
| Principais autores: | , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
Frontiers Media S.A.
2021-06-01
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| coleção: | Frontiers in Immunology |
| Assuntos: | |
| Acesso em linha: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.621153/full |
| _version_ | 1831826398895931392 |
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| author | Yanan Wu Nianzhi Zhang Keiichiro Hashimoto Chun Xia Johannes M. Dijkstra |
| author_facet | Yanan Wu Nianzhi Zhang Keiichiro Hashimoto Chun Xia Johannes M. Dijkstra |
| author_sort | Yanan Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T01:43:03Z |
| format | Article |
| id | doaj.art-502bfc837c8c4edcb15790eae1f30b29 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T01:43:03Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-502bfc837c8c4edcb15790eae1f30b292022-12-21T18:04:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.621153621153Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came FirstYanan Wu0Nianzhi Zhang1Keiichiro Hashimoto2Chun Xia3Johannes M. Dijkstra4Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaInstitute for Comprehensive Medical Science, Fujita Health University, Toyoake, JapanDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaInstitute for Comprehensive Medical Science, Fujita Health University, Toyoake, JapanStructures 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.621153/fullMHCevolutionstructureclass IIclass Ib2-microglobulin |
| spellingShingle | Yanan Wu Nianzhi Zhang Keiichiro Hashimoto Chun Xia Johannes M. Dijkstra Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First Frontiers in Immunology MHC evolution structure class II class I b2-microglobulin |
| title | Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First |
| title_full | Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First |
| title_fullStr | Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First |
| title_full_unstemmed | Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First |
| title_short | Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First |
| title_sort | structural comparison between mhc classes i and ii in evolution a class ii like molecule probably came first |
| topic | MHC evolution structure class II class I b2-microglobulin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.621153/full |
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