scholarly journals Differential patterns of diversity at neutral and adaptive loci in endangered Rhodeus pseudosericeus populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hari Won ◽  
Hyung-Bae Jeon ◽  
Dong-Young Kim ◽  
Ho Young Suk
Keyword(s):  
Mhc Class Ii ◽  
Peptide Binding ◽  
Antigenic Peptides ◽  
Spatial Continuity ◽  
Han River ◽  
Allelic Distribution ◽  
Neutral Genetic Variation ◽  
Major Factors ◽  
Degree Of Differentiation ◽  
Three Rivers

AbstractGiven the fact that threatened species are often composed of isolated small populations, spatial continuity or demography of the populations may be major factors that have shaped the species’ genetic diversity. Thus, neutral loci have been the most commonly-used markers in conservation genetics. However, the populations under the influence of different environmental factors may have evolved in response to different selective pressures, which cannot be fully reflected in neutral genetic variation. Rhodeus pseudosericeus, a bitterling species (Acheilognathidae; Cypriniformes) endemic to the Korean Peninsula, are only found in some limited areas of three rivers, Daecheon, Han and Muhan, that flow into the west coast. Here, we genotyped 24 microsatellite loci and two loci (DAB1 and DAB3) of MHC class II peptide-binding β1 domain for 222 individuals collected from seven populations. Our microsatellite analysis revealed distinctive differentiation between the populations of Daecheon and Muhan Rivers and the Han River populations, and populations were structured into two subgroups within the Han River. Apparent positive selection signatures were found in the peptide-binding residues (PBRs) of the MHC loci. The allelic distribution of MHC showed a degree of differentiation between the populations of Daecheon and Muhan Rivers and the Han River populations, partially similar to the results obtained for microsatellites, however showed rather complex patterns among populations in the Han River. Considering the apparent differences in the distribution of supertypes obtained based on the physicochemical differences induced by the polymorphisms of these PBRs, the differentiation in DAB1 between the two regional groups may result in the differences in immune function. No differentiation between these two regions was observed in the supertyping of DAB3, probably indicating that only DAB1 was associated with the response to locally specialized antigenic peptides.

scholarly journals Pathogen diversity drives the evolution of promiscuous peptide binding of human MHC-II alleles

2018 ◽  
Author(s):  
Máté Manczinger ◽  
Gábor Boross ◽  
Lajos Kemény ◽  
Viktor Müller ◽  
Tobias L. Lenz ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Peptide Binding ◽  
Class Ii ◽  
Immune Defense ◽  
Immune Gene ◽  
Antigenic Peptides ◽  
Mhc Molecules ◽  
Geographical Regions ◽  
Epitope Binding ◽  
Promiscuous Peptide

Major histocompatibility complex (MHC) molecules mediate the adaptive immune response against pathogens. Certain MHC alleles are generalists: they present an exceptionally large variety of antigenic peptides. However, the functional implications of such elevated epitope binding promiscuity in the MHC molecules are largely unknown. According to what we term the pathogen-driven promiscuity hypothesis, exposure to a broad range of pathogens favors the evolution of highly promiscuous MHC variants. Consistent with this hypothesis, we found that in pathogen-rich geographical regions, humans are more likely to carry promiscuous MHC class II DRB1 alleles, and the switch between high and low promiscuity levels has occurred repeatedly and in a rapid manner during human evolution. We also show that selection for promiscuous peptide binding shapes MHC genetic diversity. In sum, our study offers a conceptually novel mechanism to explain the global distribution of allelic variants of a key human immune gene by demonstrating that pathogen pressure maintains promiscuous MHC class II alleles. More generally, our work highlights the hitherto neglected role of epitope binding promiscuity in immune defense, with implications for medical genetics and epidemiology.

scholarly journals pH-dependent Peptide Binding Properties of the Type I Diabetes–associated I-Ag7 Molecule: Rapid Release of CLIP at an Endosomal pH

1999 ◽  
Vol 189 (11) ◽  
pp. 1723-1734 ◽  
Author(s):  
Dorothee H.F. Hausmann ◽  
Bei Yu ◽  
Stefan Hausmann ◽  
Kai W. Wucherpfennig
Keyword(s):  
Mhc Class Ii ◽  
Type I Diabetes ◽  
Peptide Binding ◽  
Sodium Dodecyl ◽  
Class Ii ◽  
Invariant Chain ◽  
Type I ◽  
Antigenic Peptides ◽  
Neutral Ph ◽  
Endosomal Ph

MHC class II molecules and invariant chain assemble at a neutral pH in the endoplasmic reticulum and are transported to a low pH compartment where the invariant chain is trimmed to the class II–associated invariant chain peptide (CLIP). For many major histocompatibility complex class II molecules, DM is required for rapid removal of CLIP, which allows binding of antigenic peptides. Since I-Ag7 confers susceptibility to type I diabetes in NOD mice, the biochemical requirements for peptide loading were examined using soluble I-Ag7 expressed in insect cells. I-Ag7 formed long-lived complexes with naturally processed peptides from transferrin and albumin, whereas several peptides that represent T cell epitopes of islet autoantigens were poor binders. I-Ag7–peptide complexes were not sodium dodecyl sulfate (SDS) resistant, indicating that SDS sensitivity may be an intrinsic property of I-Ag7. Complexes of I-Ag7 and CLIP formed at a neutral pH, but rapidly dissociated at pH 5. This rapid dissociation was due to a poor fit of M98 of CLIP in the P9 pocket of I-Ag7, since substitution of M98 by a negatively charged residue greatly enhanced the stability of the complex. These biochemical properties of I-Ag7 result in the rapid generation of empty molecules at an endosomal pH and have a global effect on peptide binding by I-Ag7.

scholarly journals H-2M molecules, like MHC class II molecules, are targeted to parasitophorous vacuoles of Leishmania-infected macrophages and internalized by amastigotes of L. amazonensis and L. mexicana

1999 ◽  
Vol 112 (15) ◽  
pp. 2559-2570
Author(s):  
J.C. Antoine ◽  
T. Lang ◽  
E. Prina ◽  
N. Courret ◽  
R. Hellio
Keyword(s):  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Large Fraction ◽  
Peptide Binding ◽  
Leishmania Species ◽  
Class Ii ◽  
Antigenic Peptides ◽  
Mouse Macrophages ◽  
Peptide Binding Groove ◽  
Binding Groove

In their amastigote stage, Leishmania are obligatory intracellular parasites of mammalian macrophages, residing and multiplying within phagolysosomal compartments called parasitophorous vacuoles (PV). These organelles have properties similar to those described for the MHC class II compartments of antigen-presenting cells, sites where peptide-class II molecule complexes are formed before their expression at the cell surface. After infection with Leishmania amazonensis or L. mexicana, endocytosis and degradation of class II molecules by intracellular amastigotes have also been described, suggesting that these parasites have evolved mechanisms to escape the potentially hazardous antigen-presentation process. To determine whether these events extend to other molecules of the antigen-presentation machinery, we have now studied the fate of the MHC molecule H-2M in mouse macrophages infected with Leishmania amastigotes. At least for certain class II alleles, H-2M is an essential cofactor, which catalyses the release of the invariant chain-derived CLIP peptide from the peptide-binding groove of class II molecules and facilitates the binding of antigenic peptides. H-2M was detected in PV of mouse macrophages infected with various Leishmania species including L. amazonensis, L. mexicana, L. major and L. donovani. PV thus contain all the molecules required for the formation of peptide-class II molecule complexes and especially of complexes with parasite peptides. The present data indicate, however, that if this process occurs, it does not lead to a clear increase of SDS-stable compact (alpha)(beta) dimers of class II. In PV that contained L. amazonensis or L. mexicana, both class II and H-2M molecules often colocalized at the level where amastigotes bind to the PV membrane, suggesting that these molecules are physically associated, directly or indirectly, and possibly interact with parasite components. Furthermore, as class II molecules, H-2M molecules were internalized by amastigotes of these Leishmania species and reached parasite compartments that also contained class II molecules. Immunostaining of H-2M within parasites was increased by treatment of infected macrophages with the cysteine protease inhibitors Z-Phe-AlaCHN2 or Z-Phe-PheCHN2 or by incubation of the parasites with the same inhibitors before infection. These data thus support the idea that amastigotes of certain Leishmania species capture and degrade some of the molecules required for antigen presentation. To examine whether endocytosis of class II molecules by the parasites occurs through interactions with parasite components involving their peptide-binding groove, we made use of the fact that a large fraction of the class II molecules of H-2M(alpha) knock-out H-2(b) mice are occupied by the peptide CLIP and are unable to bind other peptides. We found that, in Leishmania-infected macrophages of these mutant mice, class II-CLIP complexes reached PV and were internalized by amastigotes. These results thus prove that endocytosis of class II molecules by amastigotes (1) is H-2M-independent and (2) does not necessarily involve the peptide-binding pocket of these molecules. Altogether, these data are compatible with an endocytic mechanism based on general properties shared by classical and non-classical class II molecules.

Peptide Binding Inhibits Aggregation of Soluble MHC Class II in Solution

IUBMB Life ◽  
1999 ◽  
Vol 48 (5) ◽  
pp. 483-491 ◽  
Author(s):  
Subhashini Arimilli ◽  
Irina Astafieva ◽  
Prabha V. Mukku ◽  
Cristina Cardoso ◽  
Shrikant Deshpande ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Peptide Binding ◽  
Class Ii

scholarly journals Magnitude of Alloresponses to MHC Class I/II Expressing Human Cardiac Myocytes Is Limited by Their Intrinsic Ability to Process and Present Antigenic Peptides

2003 ◽  
Vol 10 (2-4) ◽  
pp. 213-226 ◽  
Author(s):  
J. Bruce Sundstrom ◽  
Kimberley C. Jollow ◽  
Veronique Braud ◽  
Francois Villinger ◽  
Andrew J. McMichael ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Influenza A ◽  
Antigen Processing ◽  
Class I ◽  
Target Cells ◽  
Mrna Levels ◽  
Antigenic Peptides ◽  
Ifn Γ

In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1) to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR β1*0301) pulsed with the influenza A matrix 1 (58-66) peptide (M1) were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC). Pretreatment of these M1-VAC targets with IFN-γ partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-γ pretreated W-1's could not process tetanus toxin (TT) or present the TT(830-843) peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-γ to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-γ pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation.

scholarly journals Machine learning reveals a non-canonical mode of peptide binding to MHC class II molecules

Immunology ◽  
2017 ◽  
Vol 152 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Massimo Andreatta ◽  
Vanessa I. Jurtz ◽  
Thomas Kaever ◽  
Alessandro Sette ◽  
Bjoern Peters ◽  
...  
Keyword(s):  
Machine Learning ◽  
Mhc Class Ii ◽  
Peptide Binding ◽  
Class Ii ◽  
Mhc Class Ii Molecules

scholarly journals DeepMHCII: A Novel Binding Core-Aware Deep Interaction Model for Accurate MHC II-peptide Binding Affinity Prediction

2021 ◽  
Author(s):  
Ronghui You ◽  
Wei Qu ◽  
Hiroshi Mamitsuka ◽  
Shanfeng Zhu
Keyword(s):  
Deep Learning ◽  
Binding Affinity ◽  
Mhc Class Ii ◽  
Large Scale ◽  
Peptide Binding ◽  
Class Ii ◽  
Biological Knowledge ◽  
Binding Interaction ◽  
Binding Core ◽  
Peptide Binding Affinity

Computationally predicting MHC-peptide binding affinity is an important problem in immunological bioinformatics. Recent cutting-edge deep learning-based methods for this problem are unable to achieve satisfactory performance for MHC class II molecules. This is because such methods generate the input by simply concatenating the two given sequences: (the estimated binding core of) a peptide and (the pseudo sequence of) an MHC class II molecule, ignoring the biological knowledge behind the interactions of the two molecules. We thus propose a binding core-aware deep learning-based model, DeepMHCII, with binding interaction convolution layer (BICL), which allows integrating all potential binding cores (in a given peptide) and the MHC pseudo (binding) sequence, through modeling the interaction with multiple convolutional kernels. Extensive empirical experiments with four large-scale datasets demonstrate that DeepMHCII significantly outperformed four state-of-the-art methods under numerous settings, such as five-fold cross-validation, leave one molecule out, validation with independent testing sets, and binding core prediction. All these results with visualization of the predicted binding cores indicate the effectiveness and importance of properly modeling biological facts in deep learning for high performance and knowledge discovery. DeepMHCII is publicly available at https://weilab.sjtu.edu.cn/DeepMHCII/.

scholarly journals MPYS, a Novel Membrane Tetraspanner, Is Associated with Major Histocompatibility Complex Class II and Mediates Transduction of Apoptotic Signals

2008 ◽  
Vol 28 (16) ◽  
pp. 5014-5026 ◽  
Author(s):  
Lei Jin ◽  
Paul M. Waterman ◽  
Karen R. Jonscher ◽  
Cindy M. Short ◽  
Nichole A. Reisdorph ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Cell Activation ◽  
Cytoplasmic Tail ◽  
Class Ii ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Death Signals

ABSTRACT Although the best-defined function of type II major histocompatibility complex (MHC-II) is presentation of antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively to cell activation or apoptotic death. MHC-II is a heterodimer of two transmembrane proteins, each containing a short cytoplasmic tail that is dispensable for transduction of death signals. This suggests the function of an undefined MHC-II-associated transducer in signaling the death response. Here we describe a novel plasma membrane tetraspanner (MPYS) that is associated with MHC-II and mediates its transduction of death signals. MPYS is unusual among tetraspanners in containing an extended C-terminal cytoplasmic tail (∼140 amino acids) with multiple embedded signaling motifs. MPYS is tyrosine phosphorylated upon MHC-II aggregation and associates with inositol lipid and tyrosine phosphatases. Finally, MHC class II-mediated cell death signaling requires MPYS-dependent activation of the extracellular signal-regulated kinase signaling pathway.

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