Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the roles of cell- and antibody-mediated immunity in urease vaccine-induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [beta2-microglobulin (-/-)] but not MHC class II knockout mice [I-Ab (-/-)]. In B cell knockout mice [microMT (-/-)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4(+) cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II-restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.
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PMID:Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses. 985 14

MHC class I proteins mediate a variety of functions in antiviral defense. In humans and mice, three MHC class I loci each contribute one or two alleles and each can present a wide variety of peptide Ags. In contrast, many lower vertebrates appear to use a single MHC class I locus. Previously we showed that a single locus was predominantly expressed in the mallard duck (Anas platyrhynchos) and that locus was adjacent to the polymorphic transporter for the Ag-processing (TAP2) gene. Characterization of a genomic clone from the same duck now allows us to compare genes to account for their differential expression. The clone carried five MHC class I genes and the TAP genes in the following gene order: TAP1, TAP2, UAA, UBA, UCA, UDA, and UEA. We designated the predominantly expressed gene UAA. Transcripts corresponding to the UDA locus were expressed at a low level. No transcripts were found for three loci, UBA, UCA, and UEA. UBA had a deletion within the promoter sequences. UCA carried a stop codon in-frame. UEA did not have a polyadenylation signal sequence. All sequences differed primarily in peptide-binding pockets and otherwise had the hallmarks of classical MHC class I alleles. Despite the presence of additional genes in the genome, the duck expresses predominantly one MHC class I gene. The limitation to one expressed MHC class I gene may have functional consequences for the ability of ducks to eliminate viral pathogens, such as influenza.
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PMID:The MHC of the duck (Anas platyrhynchos) contains five differentially expressed class I genes. 1627 26

An unprecedented level of sequence diversity has been maintained in the salmonid major histocompatibility complex (MHC) class I UBA gene, with between lineage AA sequence identities as low as 34%. The derivation of deep allelic lineages may have occurred through interlocus exon shuffling or convergence of ancient loci with the UBA locus, but until recently, no such ancient loci were uncovered. Herein, we document the existence of eight additional MHC class I loci in salmon (UCA, UDA, UEA, UFA, UGA, UHA, ULA, and ZE), six of which share exon 2 and 3 lineages with UBA, and three of which have not been described elsewhere. Half of the UBA exon 2 lineages and all UBA exon 3 lineages are shared with other loci. Two loci, UGA and UEA, share only a single exon lineage with UBA, likely generated through exon shuffling. Based on sequence homologies, we hypothesize that most exchanges and duplications occurred before or during tetraploidization (50 to 100 Ma). Novel loci that share no relationship with other salmonid loci are also identified (UHA and ZE). Each locus is evaluated for its potential to function as a class Ia gene based on gene expression, conserved residues and polymorphism. UBA is the only locus that can indisputably be classified as a class Ia gene, although three of the eight loci (ZE, UCA, and ULA) conform in three out of four measures. We hypothesize that these additional loci are in varying states of degradation to class Ib genes.
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PMID:The salmonid MHC class I: more ancient loci uncovered. 1679 19

A major challenge facing studies of major histocompatibility complex (MHC) evolution in birds is the difficulty in genotyping alleles at individual loci, and the consequent inability to investigate sequence variation and selection pressures for each gene. In this study, four MHC class I loci were isolated from the red-billed gull (Larus scopulinus), representing both the first characterized MHCI genes within Charadriiformes (shorebirds, gulls, and allies) and the first full-length MHCI sequences described outside Galloanserae (gamebirds + waterfowl). Complete multilocus genotypes were obtained for 470 individuals using a combination of reference-strand conformation analysis and direct sequencing of gene-specific amplification products, and variation of peptide-binding region (PBR) exons was surveyed for all loci. Each gene is transcribed and has conserved sequence features characteristic of antigen-presenting MHCI molecules. However, higher allelic variation, a more even allele frequency distribution, and evidence of positive selection acting on a larger number of PBR residues suggest that only one locus (Lasc-UAA) functions as a major classical MHCI gene. Lasc-UBA, with more limited variation and PBR motifs that encompass a subset of Lasc-UAA diversity, was assigned a putative minor classical function, whereas the divergent and largely invariant binding-groove motifs of Lasc-UCA and -UDA are suggestive of nonclassical loci with specialized ligand-binding roles.
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PMID:Characterization and locus-specific typing of MHC class I genes in the red-billed gull (Larus scopulinus) provides evidence for major, minor, and nonclassical loci. 2132 6

In many nonmammalian vertebrates, the genomic organization of the MHC class I region leads to biased expression of a single classical MHC class I gene coevolving with TAP transporters, whereas class I genes are poorly expressed. This contrasts to the three codominantly expressed classical MHC class I genes in humans and mice. In a sequenced haplotype from White Pekin duck, Anas platyrhynchos, there is one predominantly expressed MHC class I, UAA, although they have five MHC class I genes in the complex, arranged TAP1-TAP2-UAA-UBA-UCA-UDA-UEA The UAA gene, situated proximal to the TAP2 gene, is expressed at levels 10-fold greater than that of another expressed gene, UDA. Three duck MHC class I genes (UBA, UCA, and UEA) are predicted to be partially or completely inactivated by promoter defects, introduction of in-frame stop codon, or the lack of a polyadenylation signal. In this study, we confirm that UBA, UCA, and UEA are indeed inactivated through genetic defects at the promoter, whereas UAA and UDA have functionally equivalent promoters. To examine promoter accessibility, we performed bisulfite sequencing and show that none of the MHC class I promoters are inactivated by methylation. We determine that UDA is differentially regulated through its 3' untranslated region. Namely, expression of UDA is downregulated by let-7 microRNA, whereas the predominantly expressed MHC class I UAA is not. Regulation of UDA by let-7 microRNA suggests that the lower expression level is maintained for its function in immunity.
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PMID:The Minor MHC Class I Gene UDA of Ducks Is Regulated by Let-7 MicroRNA. 2743 Jul 16