A bony fish immunological receptor of the NITR multigene family mediates allogeneic recognition.
Ontology highlight
ABSTRACT:
SUBMITTER: Cannon JP
PROVIDER: S-EPMC2603606 | biostudies-literature | 2008 Aug
REPOSITORIES: biostudies-literature
Publications
A bony fish immunological receptor of the NITR multigene family mediates allogeneic recognition.
Cannon John P JP Haire Robert N RN Magis Andrew T AT Eason Donna D DD Winfrey Kelley N KN Hernandez Prada Jose A JA Bailey Kate M KM Jakoncic Jean J Litman Gary W GW Ostrov David A DA
Immunity 20080731 2
Novel immune-type receptors (NITRs) comprise an exceptionally large, diversified family of activating and inhibitory receptors that has been identified in bony fish. Here, we characterized the structure of an activating NITR that is expressed by a cytotoxic natural killer (NK)-like cell line and that specifically binds an allogeneic B cell target. A single amino acid residue within the NITR immunoglobulin variable (V)-type domain accounts for specificity of the interaction. Structures solved by ...[more]
Similar Datasets
Project description:In this review, we present an overview of the recent advances of genomic technologies applied to studies of fish species belonging to the superclass of Osteichthyes (bony fish) with a major emphasis on the infraclass of Teleostei, also called teleosts. This superclass that represents more than 50% of all known vertebrate species has gained considerable attention from genome researchers in the last decade. We discuss many examples that demonstrate that this highly deserved attention is currently leading to new opportunities for answering important biological questions on gene function and evolutionary processes. In addition to giving an overview of the technologies that have been applied for studying various fish species we put the recent advances in genome research on the model species zebrafish and medaka in the context of its impact for studies of all fish of the superclass of Osteichthyes. We thereby want to illustrate how the combined value of research on model species together with a broad angle perspective on all bony fish species will have a huge impact on research in all fields of fundamental science and will speed up applications in many societally important areas such as the development of new medicines, toxicology test systems, environmental sensing systems and sustainable aquaculture strategies.
| S-EPMC3954040 | biostudies-other
Project description:Modifications of the Plasmodium falciparum-infected red blood cell (iRBC) surface have been linked to parasite-associated pathology. Such modifications enable the parasite to establish long-lasting chronic infection by evading antibody mediate immune recognition and splenic clearance. With the exception of the well-demonstrated roles of var-encoded PfEMP1 in virulence and immune evasion, the biological significance of other variant surface antigens (rif and stevor) is largely unknown. While PfEMP1 and RIFIN have been located on the iRBC surface, recent studies have located STEVOR at the iRBC membrane where it may be exposed on the erythrocyte surface. To investigate the role of STEVOR in more detail, we have developed antibodies against two putative STEVOR proteins and used a combination of indirect immunofluorescence assays (IFA), live IFA, flow cytometry, as well as agglutination assays, which enable us to demonstrate that STEVOR is clonally variant at the surface of schizont stage parasites. Crucially, expression of different STEVOR on the surface of the iRBC changes the antigenic property of the parasite. Taken together, our data for the first time demonstrate that STEVOR plays a role in creating antigenic diversity of schizont stage parasites, thereby adding additional complexity to the immunogenic properties of the iRBC. Furthermore, it clearly demonstrates that to obtain a complete understanding of how parasite-induced pathology is linked to variation on the surface of the iRBC, focusing the interactions of multiple multigene families needs to be considered.
| S-EPMC2637975 | biostudies-literature
Project description:Class switch recombination was the last of the lymphocyte-specific DNA modification reactions to appear in the evolution of the adaptive immune system. It is absent in cartilaginous and bony fish, and it is common to all tetrapods. Class switching is initiated by activation-induced cytidine deaminase (AID), an enzyme expressed in cartilaginous and bony fish that is also required for somatic hypermutation. Fish AID differs from orthologs found in tetrapods in several respects, including its catalytic domain and carboxy-terminal region, both of which are essential for the switching reaction. To determine whether evolution of class switch recombination required alterations in AID, we assayed AID from Japanese puffer and zebra fish for class-switching activity in mouse B cells. We find that fish AID catalyzes class switch recombination in mammalian B cells. Thus, AID had the potential to catalyze this reaction before the teleost and tetrapod lineages diverged, suggesting that the later appearance of a class-switching reaction was dependent on the evolution of switch regions and multiple constant regions in the IgH locus.
| S-EPMC2212934 | biostudies-literature
Project description:PurposeDiagnostic tests for allergen sensitization should reflect real exposure. We made 6 new bony fish extracts, which are consumed popularly in Korea, and evaluated their allergenicity and stability.MethodsWe manufactured fish extracts from codfish, mackerel, common eel, flounder, cutlass, and catfish. Protein and parvalbumin (PV) were evaluated by Bradford assay, 2-site enzyme-linked immunosorbent assay, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and anti-PV immunoblotting. The immunoglobulin E (IgE) reactivities of the extracts were evaluated with ImmunoCAP and IgE immunoblotting using sera from 24 Korean fish allergy patients, 5 asymptomatic sensitizers, and 11 non-atopic subjects. Stability of the extracts stored in 4 different buffers were evaluated for up to a year.ResultsThe protein concentrations of commercial SPT fish extracts varied with up to a 7.5-fold difference. SDS-PAGE showed marked differences in the PV concentrations of commercial SPT reagents. Specific IgE measurements for the following investigatory fish extracts-iCodfish, iMackerel, and iEel-were concordant with that of their corresponding Phadia ImmunoCAP measurements. ImmunoCAP results showed marked IgE cross-reactivity among the fish species, and the overall sensitivity of ImmunoCAP with the investigatory fish extracts for identification of culprit fish species was 85.7%. The protein and PV concentrations in the investigatory extracts were highly stable in saline with 0.3% phenol-50% glycerol at 4°C for up to a year.ConclusionsThe commercial SPT fish extracts exhibited considerable variation in terms of allergenicity, which may impact on diagnostic accuracy. Our new fish extracts have sufficient allergenicity and stability and may be adequate to various clinical applications.
| S-EPMC8255345 | biostudies-literature
Project description:A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.
| S-EPMC4810166 | biostudies-literature
Project description:Caspase-8, a member of the caspase family, plays an important role in apoptotic signal transduction in mammals. Here we report the identification and characterization of the caspase-8 (casp8) gene in the zebrafish Danio rerio. The zebrafish casp8 gene has a genomic organization similar to mammalian casp8 genes, consisting of 10 exons. By chromosome mapping, we found that casp8 maps on linkage group 6 (LG6), a zebrafish chromosome segment orthologous to the long arm of human Chr. 2, which carries CASP8. In contrast, the zebrafish casp10-like gene and the cflar gene separately localize on LG9 and LG11, respectively, and these genes form a cluster with CASP8 on the human chromosome. This chromosomal segregation is unique to fish but not other vertebrates. Furthermore, we examined the function of zebrafish Casp8 protein in mammalian cells, and showed that it has pro-apoptotic activity when overexpressed. In addition, this molecule was capable of transmitting apoptotic signals mediated through not only Fas but also the TNF receptor in mouse Casp8-deficient cells. Expression analysis showed that casp8 is maternally expressed, and transcripts continue to be present throughout embryogenesis and into larval stages. These results show that zebrafish casp8 has a structure and function similar to mammalian CASP8 orthologs, and our study suggests that the role of caspase-8 in the apoptotic signal pathway has been conserved over at least 450 million years of vertebrate evolution.
| S-EPMC2064871 | biostudies-literature
Project description:BackgroundViruses can impose energetic demands on organisms they infect, in part by hosts mounting resistance. Recognizing that oxygen uptake reliably indicates steady-state energy consumption in all vertebrates, we comprehensively evaluated oxygen uptake and select transcriptomic messaging in sockeye salmon challenged with either a virulent rhabdovirus (IHNV) or a low-virulent reovirus (PRV). We tested three hypotheses relating to the energetic costs of viral resistance and tolerance in this vertebrate system: (1) mounting resistance incurs a metabolic cost or limitation, (2) induction of the innate antiviral interferon system compromises homeostasis, and (3) antiviral defenses are weakened by acute stress.ResultsIHNV infections either produced mortality within 1-4 weeks or the survivors cleared infections within 1-9 weeks. Transcription of three interferon-stimulated genes (ISGs) was strongly correlated with IHNV load but not respiratory performance. Instead, early IHNV resistance was associated with a mean 19% (95% CI = 7-31%; p = 0.003) reduction in standard metabolic rate. The stress of exhaustive exercise did not increase IHNV transcript loads, but elevated host inflammatory transcriptional signaling up to sevenfold. For PRV, sockeye tolerated high-load systemic PRV blood infections. ISG transcription was transiently induced at peak PRV loads without associated morbidity, microscopic lesions, or major changes in aerobic or anaerobic respiratory performance, but some individuals with high-load blood infections experienced a transient, minor reduction in hemoglobin concentration and increased duration of excess post-exercise oxygen consumption.ConclusionsContrary to our first hypothesis, effective resistance against life-threatening rhabdovirus infections or tolerance to high-load reovirus infections incurred minimal metabolic costs to salmon. Even robust systemic activation of the interferon system did not levy an allostatic load sufficient to compromise host homeostasis or respiratory performance, rejecting our second hypothesis that this ancient innate vertebrate antiviral defense is itself energetically expensive. Lastly, an acute stress experienced during testing did not weaken host antiviral defenses sufficiently to promote viral replication; however, a possibility for disease intensification contingent upon underlying inflammation was indicated. These data cumulatively demonstrate that fundamental innate vertebrate defense strategies against potentially life-threatening viral exposure impose limited putative costs on concurrent aerobic or energetic demands of the organism.
| S-EPMC8276435 | biostudies-literature
Project description:Human neutrophils express several distinct guanine nucleotide binding (G)-protein-coupled receptors that mediate their responsiveness to chemoattractants. Phosphorylation by receptor-specific and second messenger-activated protein kinases is a common mechanism for regulation of G-protein-coupled receptors. To explore the possibility that chemoattractant receptors are regulated by unique receptor kinases, we utilized PCR to identify receptor kinases in human neutrophils. Here, we report the isolation of three G-protein-coupled-receptor-kinase (GPRK)-like sequences termed GPRK5, GPRK6, and GPRK7 in addition to the beta-adrenergic receptor kinase (beta ARK) 1 and 2 isoforms (beta ARK1 and beta ARK2). Two, GPRK5 and GPRK6, showed high homology at the amino acid level to the recently identified receptor-kinase-like sequence localized close to the Huntington disease locus. GPRK7 is of interest in that it contains a DLG (Asp-Leu-Gly) amino acid motif of receptor kinases preceded by a DFD (Asp-Phe-Asp) motif. We isolated cDNAs corresponding to GPRK6; the complete sequence shows > 66% identity and 81% similarity at the amino acid level to the GPRK from the Huntington disease locus. The GPRK6 cDNA probe hybridizes to two mRNAs of 2.9 and 2.1 kb that were expressed in all the tested human tissues including HL-60 cells and neutrophils. Genomic Southern blot analysis and chromosome mapping showed that GPRK6 hybridizes to two closely related genes located on chromosomes 5 and 13 and are, therefore, distinct from the GPRK located near the Huntington disease locus on chromosome 4. The identification herein of three putative receptor kinases indicates that in addition to beta ARK and rhodopsin kinase subfamilies, there are other receptor-kinase subfamilies that regulate the broad spectrum of G-protein-coupled receptors.
| S-EPMC47575 | biostudies-other
Project description:Wnt signaling regulates physiological processes ranging from cell differentiation to bone formation. Dysregulation of Wnt signaling is linked to several human ailments, including colorectal, pancreatic, and breast cancers. As such, modulation of this pathway has been an attractive strategy for therapeutic development of anticancer agents. Since the discovery of Wnt proteins more than 35 years ago, research efforts continue to focus on understanding the biochemistry of their molecular interactions and their biological functions. Wnt is a secreted glycoprotein covalently modified with a cis-unsaturated fatty acyl group at a conserved serine residue, and this modification is required for Wnt secretion and activity. To initiate signaling, Wnt proteins bind to cell-surface Frizzled (FZD) receptors, but the molecular basis for recognition of Wnt's fatty acyl moiety by the extracellular cysteine-rich domain of FZD has become clear only very recently. Here, we review the most recent developments in the field, focusing on structural and biochemical studies of the FZD receptor family and highlighting new insights into their molecular arrangement and mode of regulation by cis-unsaturated fatty acids. Additionally, we examine how other lipid-binding proteins recognize fatty acyl chains on Wnt proteins in the regulation of Wnt secretion and activities. Altogether, this perspective expands our understanding of fatty acid-protein interactions in the FZD system and provides a basis for guiding future research in the field.
| S-EPMC6333880 | biostudies-literature
Project description:BACKGROUND: A Paramecium tetraurelia pilot genome project, the subsequent sequencing of a Megabase chromosome as well as the Paramecium genome project aimed at gaining insight into the genome of Paramecium. These cells display a most elaborate membrane trafficking system, with distinct, predictable pathways in which actin could participate. Previously we had localized actin in Paramecium; however, none of the efforts so far could proof the occurrence of actin in the cleavage furrow of a dividing cell, despite the fact that actin is unequivocally involved in cell division. This gave a first hint that Paramecium may possess actin isoforms with unusual characteristics. The genome project gave us the chance to search the whole Paramecium genome, and, thus, to identify and characterize probably all actin isoforms in Paramecium. RESULTS: The ciliated protozoan, P. tetraurelia, contains an actin multigene family with at least 30 members encoding actin, actin-related and actin-like proteins. They group into twelve subfamilies; a large subfamily with 10 genes, seven pairs and one trio with > 82% amino acid identity, as well as three single genes. The different subfamilies are very distinct from each other. In comparison to actins in other organisms, P. tetraurelia actins are highly divergent, with identities topping 80% and falling to 30%. We analyzed their structure on nucleotide level regarding the number and position of introns. On amino acid level, we scanned the sequences for the presence of actin consensus regions, for amino acids of the intermonomer interface in filaments, for residues contributing to ATP binding, and for known binding sites for myosin and actin-specific drugs. Several of those characteristics are lacking in several subfamilies. The divergence of P. tetraurelia actins and actin-related proteins between different P. tetraurelia subfamilies as well as with sequences of other organisms is well represented in a phylogenetic tree, where P. tetraurelia sequences only partially cluster. CONCLUSION: Analysis of different features on nucleotide and amino acid level revealed striking differences in isoforms of actin and actin-related proteins in P. tetraurelia, both within the organism and in comparison to other organisms. This diversification suggests unprecedented specification in localization and function within a unicellular eukaryote.
| S-EPMC1852557 | biostudies-literature