Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope.

ABSTRACT: Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8⁺ T-cell-mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I-β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV-PA_123-130 We determined the structure of the BF2*1501-PA_123-130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA_123-130 epitope in the chicken B15 lineage. Conformational characteristics of the PA_123-130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8⁺ T cells specific for the HPAIV-PA_123-130 epitope in peptide-immunized chickens indicated that a repertoire of CD8⁺ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA_123-130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.

SUBMITTER: Li X

PROVIDER: S-EPMC7170506 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Complex assembly, crystallization and preliminary X-ray crystallographic analysis of the chicken MHC class I molecule BF2*1501.

Project description:The chicken major histocompatibility complex (MHC) class I molecules named BF are strongly associated with Marek's disease (MD). A single structure, that of chicken BF2*2101 from the B21 haplotype, which might provide resistance to MD, has been determined. However, little is known about other structures apart from BF2*2101. In order to provide further structures of chicken MHC class I molecules, BF2*1501 and chicken ?(2)-microglobulin complexed with a nonapeptide (MDV-MEQ(RRR9)) derived from Marek's disease virus MEQ protein (MDV EcoRI Q fragment, residues 72-80) were assembled and crystallized. Diffraction data from the crystal were collected to 2.6 Å resolution; the crystal belonged to space group P3(1)21, with unit-cell parameters a = 125.1, b = 125.1, c = 80.9 Å and two molecules in the asymmetric unit. The Matthews coefficient V(M) was 2.08 Å(3) Da(-1), with a calculated solvent content of 40.78%. These data will be helpful in obtaining insight into the structural basis of the involvement of BF2*1501 in MD.

| S-EPMC3564611 | biostudies-literature

Antigen presentation by B cells enables epitope spreading across an MHC barrier

Project description:A progressive increase in the breadth and specificity of autoantibodies over time, termed epitope spreading, drives pathogenic targeting of an ever-widening repertoire of self-components in many autoimmune diseases. Ostensibly, this progressive inclusion of additional B cell clones into an ongoing autoreactive response can occur through linked recognition, whereby proto-autoreactive B cells recognize distinct antigenic epitopes, which carry shared T cell epitopes. In a murine model displaying epitope spreading resembling that observed in systemic lupus erythematosus, we find that the epitope spreading process is compartmentalized by MHC. Antigen presentation by B cells carrying two MHC haplotypes can bridge the MHC barrier between two compartments of B cells that do not share MHC haplotypes, by communicating with two separate pools of MHC-restricted T cells. This leads to inclusion of distinct and diverse B cell reactivities in germinal centers. Our findings demonstrate a formidable capacity of B cells to drive the autoreactive response.

2022-07-01 | GSE202358 | GEO

Multiple Structures Disclose the Secretins' Secrets.

Project description:Bacterial secretins are outer membrane proteins that provide a path for secreted proteins to access the cell exterior/surface. They are one of the core components of secretion machines and are found in type II and type III secretion systems (T2SS and T3SS, respectively). The secretins comprise giant ring-shaped homo-oligomers whose precise atomic organization was only recently deciphered thanks to spectacular developments in cryo-electron microscopy (cryo-EM) imaging techniques.

| S-EPMC5809689 | biostudies-literature

Narrow groove and restricted anchors of MHC class I molecule BF2*0401 plus peptide transporter restriction can explain disease susceptibility of B4 chickens.

Project description:The MHC has genetic associations with many diseases, often due to differences in presentation of antigenic peptides by polymorphic MHC molecules to T lymphocytes of the immune system. In chickens, only a single classical class I molecule in each MHC haplotype is expressed well due to coevolution with the polymorphic TAPs which means that resistance and susceptibility to infectious pathogens are particularly easy to observe. Previously, structures of chicken MHC class I molecule BF2*2101 from B21 haplotype showed an unusually large peptide-binding groove that accommodates a broad spectrum of peptides to present as epitopes to CTLs, explaining the MHC-determined resistance of B21 chickens to Marek's disease. In this study, we report the crystal structure of BF2*0401 from the B4 (also known as B13) haplotype, showing a highly positively charged surface hitherto unobserved in other MHC molecules, as well as a remarkably narrow groove due to the allele-specific residues with bulky side chains. Together, these properties limit the number of epitope peptides that can bind this class I molecule. However, peptide-binding assays show that in vitro, BF2*0401 can bind a wider variety of peptides than are found on the surface of B4 cells. Thus, a combination of the specificities of the polymorphic TAP and the MHC results in a very limited set of BF2*0401 peptides with negatively charged anchors to be presented to T lymphocytes.

| S-EPMC5018395 | biostudies-literature

Construction and functional test of a chicken MHC-I (BF2*15)/peptide tetramer.

Project description:The major histocompatibility complex class I (MHC class I) peptide tetramer is a sensitive and valuable tool to evaluate antigen-specific cytotoxic T lymphocytes (CTLs) of many animal species. To date, no chicken MHC class I peptide tetramer has been reported. In this report, we describe construction and functional evaluation of a chicken MHC-I (BF2*15)/peptide tetramer. To construct the chicken MHC class I peptide tetramer, genes of the chicken MHC-I alpha chain (BF2*15) and beta2 microglobulin (Chbeta2m) were synthesized by RT-PCR from the total RNA of PBMCs and the signal sequences were deleted. The BF2*15 was then fused with the BirA substrate peptide (BSP) sequence at the C terminus. Next, the synthesized PCR products of BF2*15 and Chbeta2m were cloned into the expression vector pET-28a (+) and expressed in Escherichia coli strain BL21 (DE3). Highly purified BF2*15-BSP heavy chain and Chbeta2m were obtained by a Ni(2+) NTA column affinity purification, yielding approximately 1.6mg of BF2*15-BSP and 2.4mg of Chbeta2m per 1g of the pelleted bacteria. The purified BF2*15-BSP heavy chain and Chbeta2m were refolded with synthetic peptide originated from infectious bronchitis virus nucleoprotein (IBV N(71-78)) in refolding buffer to generate the monomer of BF2*15/peptide complex. The monomer was then biotinylated and tetramerized using PE-labeled streptavidin. Upon functional evaluation of the construct by using flowcytometry, we observed that 3.65% of CTLs were specific to IBV nucleoprotein. This demonstrates that the CTL response of IBV-infected chicks could effectively be evaluated using the prepared MHC-I BF2*15/peptide tetramer.

| S-EPMC7126500 | biostudies-literature

MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.

Project description:T cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1(214-224) epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design.

| S-EPMC2954893 | biostudies-literature

Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies.

Project description:We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus containing A/Vietnam/1203/04 (H5N1) deltaHA and neuraminidase genes in the genetic background of A/Puerto Rico/8/34 (H1N1) virus. The mutants were selected with a panel of eight anti-HA monoclonal antibodies (MAbs), seven to A/Vietnam/1203/04 (H5N1) virus and one to A/Chicken/Pennsylvania/8125/83 (H5N2) virus, and the mutants' HA genes were sequenced. The amino acid changes suggested three MAb groups: four MAbs reacted with the complex epitope comprising parts of the antigenic site B of H3 HA and site Sa of H1 HA, two MAbs reacted with the epitope corresponding to the antigenic site A in H3 HA, and two MAbs displayed unusual behavior: each recognized amino acid changes at two widely separate antigenic sites. Five changes were detected in amino acid residues not previously reported as changed in H5 escape mutants, and four others had substitutions not previously described. The HA antigenic structure differs substantially between A/Vietnam/1203/04 (H5N1) virus and the low-pathogenic A/Mallard/Pennsylvania/10218/84 (H5N2) virus we previously characterized (N. V. Kaverin et al., J. Gen. Virol. 83:2497-2505, 2002). The hemagglutination inhibition reactions of the MAbs with recent highly pathogenic H5N1 viruses were consistent with the antigenic-site amino acid changes but not with clades and subclades based on H5 phylogenetic analysis. These results provide information on the recognition sites of the MAbs widely used to study H5N1 viruses and demonstrate the involvement of the HA antigenic sites in the evolution of highly pathogenic H5N1 viruses, findings that can be critical for characterizing pathogenesis and vaccine design.

| S-EPMC2169086 | biostudies-literature

Curcuminoid-BF2 complexes: Synthesis, fluorescence and optimization of BF2 group cleavage.

Project description:Eight difluoroboron complexes of curcumin derivatives carrying alkyne groups containing substituents have been synthesized following an optimised reaction pathway. The complexes were received in yields up to 98% and high purities. Their properties as fluorescent dyes have been investigated. Furthermore, a strategy for the hydrolysis of the BF2 group has been established using aqueous methanol and sodium hydroxide or triethylamine.

| S-EPMC5669223 | biostudies-literature

Antigen presentation by B cells enables epitope spreading across an MHC barrier

Project description:Antigen presentation by B cells enables epitope spreading across an MHC barrier

| PRJNA835703 | ENA

MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway.

Project description:Major histocompatibility complex class II (MHC II) expression and turn-over are regulated via its ubiquitination by the membrane associated RING-CH 1 (MARCH1) E3 ligase. Unexpectedly, we show that MHC II ubiquitination also impacts MHC I. Lack of MARCH1 in B cells and dendritic cells (DCs) resulted in a significant reduction in surface MHC I expression. This decrease was not directly caused by changes in MARCH1 ubiquitination of MHC I but indirectly by altered MHC II trafficking in the absence of its ubiquitination. Deletion of MHC II in March1-/- cells restored normal MHC I surface expression and replacement of wild type MHC II by a variant that could not be ubiquitinated caused a reduction in MHC I expression. Furthermore, these cells displayed inefficient presentation of peptide and protein antigen via MHC I to CD8+ T cells. In summary, we describe an unexpected intersection between MHC I and MHC II such that the surface expression of both molecules are indirectly and directly regulated by MARCH1 ubiquitination, respectively.

| S-EPMC6042767 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data