Ancient features of the MHC class II presentation pathway, and a model for the possible origin of MHC molecules

Dijkstra, Johannes M.; Yamaguchi, Takuya

doi:10.1007/s00251-018-1090-2

Cited by 30 publications

(25 citation statements)

References 125 publications

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“…The length of the amino acid sequence of Xela-UAAg is markedly different from that of MHC-I sequences in mammals (49). The comparison of the classical MHC-I amino acid sequences between X. laevis and mammals, chickens, and fish revealed ,45% sequence identity (17,50). Thus, the differences in amino acid sequences and lengths between species are very significant.…”

Section: Discussionmentioning

confidence: 92%

A Glimpse of the Peptide Profile Presentation by Xenopus laevis MHC Class I: Crystal Structure of pXela-UAA Reveals a Distinct Peptide-Binding Groove

Zhang

et al. 2020

The Journal of Immunology

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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 ∼3.8Å 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.

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Section: Discussionmentioning

confidence: 92%

A Glimpse of the Peptide Profile Presentation by Xenopus laevis MHC Class I: Crystal Structure of pXela-UAA Reveals a Distinct Peptide-Binding Groove

Zhang

et al. 2020

The Journal of Immunology

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“…In the present study, we first identified a novel BC prognosis-associated pseudogene HLA-DPB2 , of which the expression, prognosis, role, and corresponding regulatory mechanisms of HLA-DPB2 in BC have not been illuminated. HLA-DPB1 , the parental gene of HLA-DPB2 , is part of human leukocyte antigen (HLA) complex and generally expressed in antigen-presenting cells ( 28 ). Previous research studies reported that its parental gene, HLA-DPB1 , can promote immunity and is essential for immunotherapy in leukemia ( 29 , 30 ).…”

Section: Introductionmentioning

confidence: 99%

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

et al. 2020

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Immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma and non-small cell lung cancer. However, many patients with breast cancer (BC) show low response to ICIs due to the paucity of infiltrating immune cells. Pseudogenes, as a particular kind of long-chain noncoding RNA, play vital roles in tumorigenesis, but their potential roles in tumor immunology remain unclear. In this study that used data from online databases, the novel pseudogene HLA-DPB2 and its parental gene HLA-DPB1 were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed that HLA-DPB2 might serve as an endogenous RNA to increase HLA-DPB1 expression by competitively binding with has-miR-370-3p . Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the HLA-DPB2/HLA-DPB1 axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of the HLA-DPB2 and HLA-DPB1 were significantly associated with high immune infiltration abundance of CD8+ T cells, CD4+ T cells, Tfh, Th1, and NK cells and with high expression of majority biomarkers of monocytes, NK cell, T cell, CD8+ T cell, and Th1 in BC and its subtype, indicating that HLA-DPB2 can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, the HLA-DPB2 and HLA-DPB1 expression levels positively correlated with the expression levels of programmed cell death protein 1, programmed cell death ligand 1, and cytotoxic T-lymphocyte-associated antigen-4. Our findings suggest that pseudogene HLA-DPB2 can upregulate HLA-DPB1 through sponging has-miR-370-3p, thus exerting its antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment, and that targeting the HLA-DPB2/HLA-DPB1 axis with ICIs may optimize the current immunotherapy for BC.

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“…The HLA-DM and HLA-DO molecules do not present peptides but have a “peptide-editing” (helping to select for high affinity peptides) function in the peptide loading system of classical MHC class II [100]. Whereas HLA-DO appears to be an evolutionary relatively young diversification from the classical MHC class II lineage, DM lineage genes can already be found in lungfish and DM lineage is stably inherited throughout tetrapod species [27,67]. Despite absence of DM, teleost MHC class II molecules can be distinguished into classical versus nonclassical based on polymorphism, expression patterns, and presence/absence of residues important for peptide ligand binding (e.g., [27,35,36,37,38]).…”

Section: Classical and Nonclassical Mhc Genesmentioning

confidence: 99%

Major Histocompatibility Complex (MHC) Genes and Disease Resistance in Fish

Yamaguchi

Dijkstra

2019

Cells

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Fascinating about classical major histocompatibility complex (MHC) molecules is their polymorphism. The present study is a review and discussion of the fish MHC situation. The basic pattern of MHC variation in fish is similar to mammals, with MHC class I versus class II, and polymorphic classical versus nonpolymorphic nonclassical. However, in many or all teleost fishes, important differences with mammalian or human MHC were observed: (1) The allelic/haplotype diversification levels of classical MHC class I tend to be much higher than in mammals and involve structural positions within but also outside the peptide binding groove; (2) Teleost fish classical MHC class I and class II loci are not linked. The present article summarizes previous studies that performed quantitative trait loci (QTL) analysis for mapping differences in teleost fish disease resistance, and discusses them from MHC point of view. Overall, those QTL studies suggest the possible importance of genomic regions including classical MHC class II and nonclassical MHC class I genes, whereas similar observations were not made for the genomic regions with the highly diversified classical MHC class I alleles. It must be concluded that despite decades of knowing MHC polymorphism in jawed vertebrate species including fish, firm conclusions (as opposed to appealing hypotheses) on the reasons for MHC polymorphism cannot be made, and that the types of polymorphism observed in fish may not be explained by disease-resistance models alone.

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Ancient features of the MHC class II presentation pathway, and a model for the possible origin of MHC molecules

Cited by 30 publications

References 125 publications

A Glimpse of the Peptide Profile Presentation by Xenopus laevis MHC Class I: Crystal Structure of pXela-UAA Reveals a Distinct Peptide-Binding Groove

A Glimpse of the Peptide Profile Presentation by Xenopus laevis MHC Class I: Crystal Structure of pXela-UAA Reveals a Distinct Peptide-Binding Groove

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

Major Histocompatibility Complex (MHC) Genes and Disease Resistance in Fish

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