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Szukiewicz D. Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity. Front Immunol 2022; 13:943839. [PMID: 35935991 PMCID: PMC9355085 DOI: 10.3389/fimmu.2022.943839] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 06/27/2022] [Indexed: 11/13/2022] Open
Abstract
Endometriosis is defined as the presence of endometrial-like glands and stroma located outside the uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% of reproductive-aged women and is a well-recognized cause of chronic pelvic pain and infertility. Despite the still unknown etiology of endometriosis, much evidence suggests the participation of epigenetic mechanisms in the disease etiopathogenesis. The main rationale is based on the fact that heritable phenotype changes that do not involve alterations in the DNA sequence are common triggers for hormonal, immunological, and inflammatory disorders, which play a key role in the formation of endometriotic foci. Epigenetic mechanisms regulating T-cell responses, including DNA methylation and posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work in concert with organ structural cells to generate appropriate immune responses and are functionally shaped by organ-specific environmental conditions. Thus, a failure to precisely regulate immune cell transcription may result in compromised immunological integrity of the organ with an increased risk of inflammatory disorders. The coexistence of endometriosis and autoimmunity is a well-known occurrence. Recent research results indicate regulatory T-cell (Treg) alterations in endometriosis, and an increased number of highly active Tregs and macrophages have been found in peritoneal fluid from women with endometriosis. Elimination of the regulatory function of T cells and an imbalance between T helper cells of the Th1 and Th2 types have been reported in the endometria of women with endometriosis-associated infertility. This review aims to present the state of the art in recognition epigenetic reprogramming of T cells as the key factor in the pathophysiology of endometriosis in the context of T-cell-related autoimmunity. The new potential therapeutic approaches based on epigenetic modulation and/or adoptive transfer of T cells will also be outlined.
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Fei C, Nie L, Zhang J, Chen J. Potential Applications of Fluorescence-Activated Cell Sorting (FACS) and Droplet-Based Microfluidics in Promoting the Discovery of Specific Antibodies for Characterizations of Fish Immune Cells. Front Immunol 2021; 12:771231. [PMID: 34868030 PMCID: PMC8635192 DOI: 10.3389/fimmu.2021.771231] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 10/21/2021] [Indexed: 11/21/2022] Open
Abstract
Akin to their mammalian counterparts, teleost fish possess a complex assortment of highly specialized immune cells that are capable of unleashing potent innate immune responses to eradicate or mitigate incoming pathogens, and also differentiate into memory lymphocytes to provide long-term protection. Investigations into specific roles and functions of fish immune cells depend on the precise separation of each cell type. Commonly used techniques, for example, density gradient centrifugation, rely on immune cells to have differing sizes or densities and thus fail to separate between similar cell types (e.g. T and B lymphocytes). Furthermore, a continuously growing database of teleost genomic information has revealed an inventory of cellular markers, indicating the possible presence of immune cell subsets in teleost fish. This further complicates the interpretation of results if subsets of immune cells are not properly separated. Consequently, monoclonal antibodies (mAbs) against specific cellular markers are required to precisely identify and separate novel subsets of immune cells in fish. In the field of fish immunology, mAbs are largely generated using the hybridoma technology, resulting in the development of mAbs against specific cellular markers in different fish species. Nevertheless, this technology suffers from being labour-intensive, time-consuming and most importantly, the inevitable loss of diversities of antibodies during the fusion of antibody-expressing B lymphocytes and myeloma cells. In light of this, the focus of this review is to discuss the potential applications of fluorescence-activated cell sorting and droplet-based microfluidics, two emerging technologies capable of screening and identifying antigen-specific B lymphocytes in a high-throughput manner, in promoting the development of valuable reagents for fish immunology studies. Our main goal is to encourage the incorporation of alternative technologies into the field of fish immunology to promote the production of specific antibodies in a high-throughput and cost-effective way, which could better allow for the precise separation of fish immune cells and also facilitate the identification of novel immune cell subsets in teleost fish.
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Affiliation(s)
- Chenjie Fei
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, China.,Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, China.,Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, China
| | - Li Nie
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, China.,Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, China.,Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, China
| | - Jianhua Zhang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, China.,Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, China.,Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, China
| | - Jiong Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, China.,Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, China.,Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, China
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3
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Medvedev AE. Toll-like receptor polymorphisms, inflammatory and infectious diseases, allergies, and cancer. J Interferon Cytokine Res 2013; 33:467-84. [PMID: 23675778 DOI: 10.1089/jir.2012.0140] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Toll-like receptors (TLRs) are germ-line-encoded innate immune sensors that recognize conserved microbial structures and host alarmins and signal expression of MHC proteins, costimulatory molecules, and inflammatory mediators by macrophages, neutrophils, dendritic cells, and other cell types. These processes activate immediate and early mechanisms of innate host defense, as well as initiate and orchestrate adaptive immune responses. Several single-nucleotide polymorphisms (SNPs) within the TLR genes have been associated with altered susceptibility to infectious, inflammatory, and allergic diseases, and have been found to play a role in tumorigenesis. Critical advances in our understanding of innate immune functions and genome-wide association studies (GWAS) have uncovered complex interactions of genetic polymorphisms within TLRs and environmental factors. However, conclusions obtained in the course of such analyses are restricted by limited power of many studies that is likely to explain controversial findings. Further, linkages to certain ethnic backgrounds, gender, and the presence of multigenic effects further complicate the interpretations of how the TLR SNPs affect immune responses. For many TLRs, the molecular mechanisms by which SNPs impact receptor functions remain unknown. In this review, I have summarized current knowledge about the TLR polymorphisms, their impact on TLR signaling, and associations with various inflammatory, infectious, allergic diseases and cancers, and discussed the directions of future scientific research.
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Affiliation(s)
- Andrei E Medvedev
- Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
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Sameshima S, Nakao M, Somamoto T. Diversity of CD2 subfamily receptors in cyprinid fishes. RESULTS IN IMMUNOLOGY 2012; 2:25-34. [PMID: 24371564 PMCID: PMC3862340 DOI: 10.1016/j.rinim.2012.01.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Revised: 01/18/2012] [Accepted: 01/24/2012] [Indexed: 01/08/2023]
Abstract
CD2 family receptor (CD2f) is evolutionarily conserved and is widely expressed by various types of leukocytes. To elucidate the phylogenetic diversity of the CD2f, we characterized CD2f in teleosts using ginbuna crucian carp and zebrafish. The identified CD2f isoforms of the ginbuna carp (caauCD2f) exhibited high sequence similarity to the mammalian CD2 subsets CD48, CD244, and CD319, but it was difficult to classify them into their respective mammalian CD2f based on sequence similarity, the presence of an immunoreceptor tyrosine-based switch motif (ITSM), and phylogenetic tree analysis. Although the four caauCD2f isoforms share an extracellular domain with quite high identity (83-94% identity at the nucleic acid level), they differ in the number of ITSM motifs in their cytoplasmic tail. RT-PCR and in situ hybridization analyses showed that the caauCD2f isoforms are expressed by different cell populations, suggesting that they, like mammalian CD2f, have diverse roles. Interestingly, immunoglobulin (Ig) domain-like sequences with high identity to caauCD2fs are clustered close together within 0.6 Mbp on zebrafish chromosomes 1 and 2 (at least 8 and 35 sequences, respectively), and many pairs of the Ig domains share more than 90% identity at the amino acid level. Therefore, the teleost CD2fs with considerably high identity have been probably generated from a common ancestral Ig-domain gene by a very recent gene duplication event. These findings suggest that the identified CD2f acquired functional diversification through successive duplications together with the acquisition of ITSM.
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Affiliation(s)
| | | | - Tomonori Somamoto
- Laboratory of Marine Biochemistry, Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan
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5
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Sakamaki K, Nozaki M, Kominami K, Satou Y. The evolutionary conservation of the core components necessary for the extrinsic apoptotic signaling pathway, in Medaka fish. BMC Genomics 2007; 8:141. [PMID: 17540041 PMCID: PMC1903365 DOI: 10.1186/1471-2164-8-141] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2007] [Accepted: 06/01/2007] [Indexed: 12/24/2022] Open
Abstract
Background Death receptors on the cell surface and the interacting cytosolic molecules, adaptors and initiator caspases, are essential as core components of the extrinsic apoptotic signaling pathway. While the apoptotic machinery governing the extrinsic signaling pathway is well characterized in mammals, it is not fully understood in fish. Results We identified and characterized orthologs of mammalian Fas, FADD and caspase-8 that correspond to the death receptor, adaptor and initiator caspase, from the Medaka fish (Oryzias latipes). Medaka Fas, caspase-8 and FADD exhibited protein structures similar to that of their mammalian counterparts, containing a death domain (DD), a death effector domain (DED) or both. Functional analyses indicated that these molecules possess killing activity in mammalian cell lines upon overexpression or following activation by apoptotic stimuli, suggesting similar pro-apoptotic functions in the extrinsic pathway as those in mammals. Genomic sequence analysis revealed that the Medaka fas (tnfrsf6), fadd and caspase-8 (casp8) genes are organized in a similar genomic structure as the mammalian genes. Database search and phylogenetic analysis revealed that the fas gene, but not the fadd and casp8 genes, appear to be present only in vertebrates. Conclusion Our results indicate that the core components necessary for the extrinsic apoptotic pathway are evolutionarily conserved in function and structure across vertebrate species. Based on these results, we presume the mechanism of apoptosis induction via death receptors was evolutionarily established during the appearance of vertebrates.
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MESH Headings
- Amino Acid Sequence
- Animals
- Apoptosis
- Base Sequence
- Caspase 8/chemistry
- Caspase 8/genetics
- Caspase 8/metabolism
- Cells, Cultured
- DNA, Complementary
- Databases, Genetic
- Embryo, Mammalian
- Embryo, Nonmammalian
- Evolution, Molecular
- Exons
- Expressed Sequence Tags
- Fas Ligand Protein/chemistry
- Fas Ligand Protein/genetics
- Fas Ligand Protein/metabolism
- Fas-Associated Death Domain Protein/chemistry
- Fas-Associated Death Domain Protein/genetics
- Fas-Associated Death Domain Protein/metabolism
- Fibroblasts/cytology
- Fibroblasts/metabolism
- Fluorescent Antibody Technique, Indirect
- Genome
- HeLa Cells
- Humans
- Immunohistochemistry
- Mice
- Molecular Sequence Data
- NIH 3T3 Cells
- Open Reading Frames
- Oryzias/genetics
- Oryzias/metabolism
- Phylogeny
- Protein Structure, Tertiary
- Receptors, Death Domain/chemistry
- Receptors, Death Domain/genetics
- Receptors, Death Domain/metabolism
- Sequence Analysis, DNA
- Sequence Homology, Amino Acid
- Signal Transduction
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Affiliation(s)
- Kazuhiro Sakamaki
- Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan
| | - Masami Nozaki
- Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan
| | - Katsuya Kominami
- Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan
- Present address: Nihon Schering Research Center, Kobe 650-0047, Japan
| | - Yutaka Satou
- Department of Zoology, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan
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Piyaviriyakul P, Kondo H, Hirono I, Aoki T. A novel immune-type receptor of Japanese flounder (Paralichthys olivaceus) is expressed in both T and B lymphocytes. FISH & SHELLFISH IMMUNOLOGY 2007; 22:467-76. [PMID: 17158066 DOI: 10.1016/j.fsi.2006.05.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2006] [Revised: 05/22/2006] [Accepted: 05/28/2006] [Indexed: 05/12/2023]
Abstract
A cDNA encoding a novel immune-type receptor (NITR) of Japanese flounder, Paralichthys olivaceus, was isolated from a kidney cDNA library. The cDNA encoded 357 amino acid residues. The amino acid sequence identities between Japanese flounder NITR1 (poNITR1) and previously reported fish NITRs were approximately 30%-40%. The poNITR1 consisted of two extracellular immunoglobulin (Ig) domains (V and V/C2), a transmembrane domain, an immunoreceptor tyrosine-based inhibitor motif (ITIM) and an ITIM-like motif (itim) in the cytoplasmic region. Five potential N-link glycosylation sites (N-X-S/T) are present in the extracellular Ig domains. Seven cysteine (Cys) residues, which are conserved in previously reported NITRs were observed in the extracellular domain of poNITR1. The poNITR1 gene is composed of five exons and four introns spanning approximately 3.4kb. The poNITR1 transcripts were mainly detected in gill, head kidney, trunk kidney, intestine, while it was weakly detected in heart, liver, muscle, peripheral blood leucocytes, skin, spleen and stomach. However, poNITR1 gene expression was not detected in muscle or ovary. NITR gene expression was not induced by LPS or poly I:C. In situ hybridization revealed that Japanese flounder NITR is expressed in both TCR-alpha- and IgM-presenting cells.
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Affiliation(s)
- Prapruddee Piyaviriyakul
- Laboratory of Genome Science, Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, Konan 4-5-7, Minato, Tokyo 108-8477, Japan
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Yu C, Dong M, Wu X, Li S, Huang S, Su J, Wei J, Shen Y, Mou C, Xie X, Lin J, Yuan S, Yu X, Yu Y, Du J, Zhang S, Peng X, Xiang M, Xu A. Genes "waiting" for recruitment by the adaptive immune system: the insights from amphioxus. THE JOURNAL OF IMMUNOLOGY 2005; 174:3493-500. [PMID: 15749885 DOI: 10.4049/jimmunol.174.6.3493] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
In seeking evidence of the existence of adaptive immune system (AIS) in ancient chordate, cDNA clones of six libraries from a protochordate, the Chinese amphioxus, were sequenced. Although the key molecules such as TCR, MHC, Ig, and RAG in AIS have not been identified from our database, we demonstrated in this study the extensive molecular evidence for the presence of genes homologous to many genes that are involved in AIS directly or indirectly, including some of which may represent the putative precursors of vertebrate AIS-related genes. The comparative analyses of these genes in different model organisms revealed the different fates of these genes during evolution. Their gene expression pattern suggested that the primitive digestive system is the pivotal place of the origin and evolution of the AIS. Our studies support the general statement that AIS appears after the jawless/jawed vertebrate split. However our study further reveals the fact that AIS is in its twilight in amphioxus and the evolution of the molecules in amphioxus are waiting for recruitment by the emergence of AIS.
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Affiliation(s)
- Cuiling Yu
- Department of Biochemistry, Guangzhou Center for Bioinformatics, College of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China
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8
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Link JM, Larson JE, Schroeder HW. Despite extensive similarity in germline DH and JH sequence, the adult Rhesus macaque CDR-H3 repertoire differs from human. Mol Immunol 2004; 42:943-55. [PMID: 15829286 DOI: 10.1016/j.molimm.2004.09.027] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2004] [Accepted: 09/21/2004] [Indexed: 11/28/2022]
Abstract
Rhesus macaques (Macaca mulatta) and chimpanzees (Pan troglodytes) are frequently used models for the study and treatment of human infectious diseases, including AIDS. Confidence in the equivalence to human of the humoral immune responses of these higher primates has grown as studies of immunoglobulin germline sequences have documented average identities of 90% or greater to human counterparts. The most variable component of the immunoglobulin heavy chain, complementarity determining region 3 (CDR-H3) is the product of somatic (junctional) as well as germline (combinatorial) mechanisms of diversity. Located at the center of the antigen binding site, CDR-H3 often exerts a dominant role in antibody specificity and affinity. To test whether similarity in germline DH and JH sequence would yield similarity in CDR-H3 composition in the expressed repertoire, we compared IgM CDR-H3 transcripts from Rhesus and chimpanzee blood to human. In fetal Rhesus, the range and mean of CDR-H3 lengths was similar to that observed in fetal human. However, the Rhesus repertoire of adult muCDR-H3 transcripts did not contain the longer hypervariable intervals that humans begin to express late in the second trimester of fetal life. Conversely, the adult chimpanzee repertoire included more long CDR-H3 structures than human. The differences between these adult repertoires reflected fine changes in N addition and terminal nucleotide loss. We conclude that the same mechanisms that refine and shape CDR-H3 diversity during ontogeny can also be used to fine tune and individualize species-specific antibody repertoires despite germline immunoglobulin sequence similarity.
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Affiliation(s)
- Jason M Link
- Division of Developmental and Clinical Immunology, Department of Microbiology, University of Alabama at Birmingham, AL 35294-3300, USA
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9
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Long S, Wilson M, Bengtén E, William Clem L, Miller NW, Gregory Chinchar V. Identification and characterization of a FasL-like protein and cDNAs encoding the channel catfish death-inducing signaling complex. Immunogenetics 2004; 56:518-30. [PMID: 15375637 PMCID: PMC1364530 DOI: 10.1007/s00251-004-0701-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2004] [Indexed: 12/13/2022]
Abstract
To elucidate cytolytic mechanisms in the channel catfish, lysates from catfish lymphoid and fibroblast cell lines were screened by Western blot analysis using a panel of antibodies reactive with components of the mammalian apoptotic pathway. Strong reactivity with three proteins (approximate Mr 70,000, 37,000, and 15,000) was seen using an antibody targeted to mammalian Fas ligand (FasL). The sizes of the two smaller proteins are consistent with their tentative designation as membrane-bound (37,000 Mr) and soluble (15,000 Mr) FasL. Treatments known to induce FasL in mammalian systems (e.g., PMA/calcium ionophore, UV-irradiation) induced expression of the 37,000- Mr protein in catfish T-cell lines. Moreover, expression of the 37,000- Mr protein in clonal T cells was up-regulated by increasing cell density. At the nucleotide level, homologues of Fas receptor (FasR), FADD, and caspase 8 were identified and characterized. These gene products likely constitute the teleost equivalent of the death-inducing signaling complex (DISC). FADD was constitutively expressed in all (T, B, macrophage, and fibroblast) cell lines examined as well as in peripheral blood lymphocytes (PBL), whereas FasR and caspase 8 were expressed in all cell lines except CCO, a FasL-positive fibroblast line. In contrast to FasL, expression of FasR and caspase 8 was inversely proportional to cell density. Collectively these studies identified four membrane-proximal proteins involved in the initiation of apoptosis in channel catfish and suggest that mechanisms of cell-mediated cytotoxicity in teleosts are similar to those used by mammals.
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Affiliation(s)
- Scott Long
- Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA e-mail: Tel.: +1-601-9841743 Fax: +1-601-9841708
| | - Melanie Wilson
- Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA e-mail: Tel.: +1-601-9841743 Fax: +1-601-9841708
| | - Eva Bengtén
- Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA e-mail: Tel.: +1-601-9841743 Fax: +1-601-9841708
| | - L. William Clem
- Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA e-mail: Tel.: +1-601-9841743 Fax: +1-601-9841708
| | - Norman W. Miller
- Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA e-mail: Tel.: +1-601-9841743 Fax: +1-601-9841708
| | - V. Gregory Chinchar
- Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA e-mail: Tel.: +1-601-9841743 Fax: +1-601-9841708
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Bartl S, Miracle AL, Rumfelt LL, Kepler TB, Mochon E, Litman GW, Flajnik MF. Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural conservation within vertebrates. Immunogenetics 2003; 55:594-604. [PMID: 14579105 DOI: 10.1007/s00251-003-0608-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2003] [Revised: 08/25/2003] [Indexed: 01/21/2023]
Abstract
The DNA polymerase (pol) X family is an ancient group of enzymes that function in DNA replication and repair (pol beta), translesion synthesis (pol lambda and pol micro) and terminal addition of non-templated nucleotides. This latter terminal deoxynucleotidyl transferase (TdT) activity performs the unique function of providing diversity at coding joins of immunoglobulin and T-cell receptor genes. The first isolated full-length TdT genes from shark and skate are reported here. Comparisons with the three-dimensional structure of mouse TdT indicate structural similarity with elasmobranch orthologues that supports both a template-independent mode of replication and a lack of strong nucleotide bias. The vertebrate TdTs appear more closely related to pol micro and fungal polymerases than to pol lambda and pol beta. Thus, unlike other molecules of adaptive immunity, TdT is a member of an ancient gene family with a clear gene phylogeny and a high degree of similarity, which implies the existence of TdT ancestors in jawless fishes and invertebrates.
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Affiliation(s)
- Simona Bartl
- Moss Landing Marine Laboratories, 8272 Moss Landing Road, CA 95039, Moss Landing, USA.
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11
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Dijkstra JM, Kiryu I, Köllner B, Yoshiura Y, Ototake M. MHC class II invariant chain homologues in rainbow trout (Oncorhynchus mykiss). FISH & SHELLFISH IMMUNOLOGY 2003; 15:91-105. [PMID: 12834614 DOI: 10.1016/s1050-4648(02)00141-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The MHC class II invariant chain (Ii or CD74) in higher vertebrates is necessary for normal MHC class II loading in endosomal compartments. Detection of an Ii chain in fish would greatly support the idea that MHC class II function in fish and higher vertebrates is similar. Before this study only Ii homologues had been reported in fish that are unlikely to perform true Ii function. In the present study two Ii-like genes, Onmy-Iclp-1 and Onmy-Iclp-2, were detected in rainbow trout. Conservation of elements, particularly in Onmy-Iclp-1, suggests that the encoded proteins may be involved in MHC class II transport and peptide loading as is the Ii protein. The expression pattern of both rainbow trout genes was similar to that of the MHC class II beta chain, with strong expression in the lymphoid tissues, gills and intestine. Analysis of separated peripheral blood leucocyte fractions indicated that expression of Onmy-Iclp-1, Onmy-Iclp-2 and the MHC class II beta chain were all highest in B lymphocytes. This agrees with the expectation that the functions of the products of the new genes are closely associated with MHC class II. It is interesting why in rainbow trout there are two proteins that may function similar to Ii in higher vertebrates.
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Affiliation(s)
- Johannes Martinus Dijkstra
- Inland Station/National Research Institute of Aquaculture, Fisheries Research Agency, Tamaki, Mie, 519-0423, Japan
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12
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13
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Dijkstra JM, Köllner B, Aoyagi K, Sawamoto Y, Kuroda A, Ototake M, Nakanishi T, Fischer U. The rainbow trout classical MHC class I molecule Onmy-UBA*501 is expressed in similar cell types as mammalian classical MHC class I molecules. FISH & SHELLFISH IMMUNOLOGY 2003; 14:1-23. [PMID: 12547623 DOI: 10.1006/fsim.2001.0407] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Onmy-UBA is a polymorphic classical major histocompatibility (MHC) class I locus in rainbow trout (Oncorhynchus mykiss). A common allomorph is Onmy-UBA*501, which has been detected in several wildtype strains, in the clonal homozygous rainbow trout C25 and, in the current study, in the rainbow trout gonad cell line RTG-2. The extracellular domain of this allomorph was expressed in E. coli and a murine monoclonal antibody designated H9 was generated against the recombinant protein. In Western blot analysis Mab H9 specifically recognised an n-glycosylated protein of 45 kDa in leucocytes and erythrocytes of C25 fish and in RTG-2 cells. The level of Onmy-UBA*501 expression in erythrocytes was very low. Immunocytochemistry of isolated cells indicated expression in lymphocytes, macrophages, neutrophils, erythrocytes, RTG-2 cells and Onmy-UBA *501 transfected CHO cells, but not in untransfected CHO cells. Immunohistochemistry using frozen sections of C25 fish indicated that Onmy-UBA*501 expression is strong in the lymphoid organs (thymus, head kidney and spleen) and in the epithelia and endothelia of several organs. No significant expression was observed in muscle fibres, hepatocytes or neurons. These observations demonstrate that in jawed fish, the lowest phylogenetic group possessing an MHC system, the classical MHC class I molecules are expressed in similar cell types as in higher vertebrates.
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Affiliation(s)
- Johannes M Dijkstra
- Immunology Section, National Research Institute of Aquaculture, Tamaki Mie, 519-0423, Japan
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Yoder JA, Hawke NA, Eason DD, Mueller MG, Davids BJ, Gillin FD, Litman GW. BIVM, a novel gene widely distributed among deuterostomes, shares a core sequence with an unusual gene in Giardia lamblia. Genomics 2002; 79:750-5. [PMID: 12036287 DOI: 10.1006/geno.2002.6768] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
A novel gene, BIVM (for basic, immunoglobulin-like variable motif-containing), has been identified using an electronic search based on the conservation of short sequence motifs within the variable region of immunoglobulin (Ig) genes. BIVM maps to human chromosome 13q32-q33 and is predicted to encode a 503-amino-acid protein with a pI of 9.1. The 5' untranslated region of BIVM is encoded in two exons; the coding portion is encoded in nine exons. BIVM is tightly linked (41 bp) and in the opposite transcriptional orientation to MGC5302 (also known as KDEL1 and EP58) in human. The ubiquitous expression of BIVM in normal tissues and the presence of a 5' CpG island suggest that BIVM is a housekeeping gene. Characterization of BIVM in representative species demonstrates significant conservation throughout deuterostomes; no sequence with significant identity to BIVM has been detected in proteostomes. However, an unusual gene has been identified in the protozoan pathogen Giardia lamblia that is similar to the core sequence of BIVM, suggesting the possibility of a horizontal gene transfer.
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Affiliation(s)
- Jeffrey A Yoder
- Department of Pediatrics, University of South Florida, Children's Research Institute, St. Petersburg, FL 33701, USA
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Sun K, Jin BQ, Feng Q, Zhu Y, Yang K, Liu XS, Dong BQ. Identification of CD226 ligand on colo205 cell surface. World J Gastroenterol 2002; 8:108-13. [PMID: 11833083 PMCID: PMC4656598 DOI: 10.3748/wjg.v8.i1.108] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To confirm the existence of CD226 ligand and its distribution, which is a novel molecule that was cloned in 1996.
METHODS: The mRNA was extracted from TPA activated Jurkat cells and used as a template for reverse-transcription. After PCR amplification, the fragment including CD226 extracellular region and the splice donor sequence “ACTTACCTGT” was obtained and cloned into fusion expression vector pIG. The recombinant vector pCD226/Ig was transfected in COS-7 cells by DEAE-Dextran method, the secreting fusion protein was identified by Sandwich ELISA, and was purified by anti-CD226 affinity chromatography. This fusion protein was used as a probe in the investigation of CD226 ligand by immunohistochemistry. Existence of CD226 ligand was further identified by adhesion experiment.
RESULTS: Expression of a secreting fusion protein was identified by sandwich ELISA, indicating that both CD226 extracellular domain and IgGFc domain could be recognized respectively by anti-CD226 and anti-hIgFc mAb. About 130 μg CD226/Ig fusion protein could be obtained from 100 mL COS-7 culture supernatants by anti-CD226 affinity chromatography purification. SDS-PAGE showed that this fusion protein has a molecular mass of 83 ku. It was confirmed by immunohistochemistry that CD226 ligand expressed on the Colo205 cells, but not on Jurkat cell, U937 cell and mixed lymphocyte culture cells. In adhesive assay, resting Jurkat cells did not have significant adhesion to Colo205 cells. In contrast, activated Jurkat cells could bind to colon carcinoma Colo205 cells and this adhesive reaction could be blocked by CD226/Ig fusion protein or anti-CD226 mAb. Immunochemical experiment showed that Colo205 cells could be specifically stained by CD226/Ig, indicating that CD226 ligand exists on the surface of Colo205 cells.
CONCLUSION: Existence of CD226 ligand on the surface of Colo205 cells was identified by immunohistochemistry and adhesion blocking experiment. In addition, the secreting CD226/Ig fusion protein prepared in this study will be a potential tool for further investigation of CD226 ligand.
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Affiliation(s)
- Kai Sun
- Department of Hepatobiliary Surgery, Xijing Hospital, Xi'an 710032, Shaanxi province, China.
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Yoder JA, Mueller MG, Wei S, Corliss BC, Prather DM, Willis T, Litman RT, Djeu JY, Litman GW. Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian leukocyte receptor cluster. Proc Natl Acad Sci U S A 2001; 98:6771-6. [PMID: 11381126 PMCID: PMC34428 DOI: 10.1073/pnas.121101598] [Citation(s) in RCA: 87] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
An extensive, highly diversified multigene family of novel immune-type receptor (nitr) genes has been defined in Danio rerio (zebrafish). The genes are predicted to encode type I transmembrane glycoproteins consisting of extracellular variable (V) and V-like C2 (V/C2) domains, a transmembrane region and a cytoplasmic tail. All of the genes examined encode immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic tail. Radiation hybrid panel mapping and analysis of a deletion mutant line (b240) indicate that a minimum of approximately 40 nitr genes are contiguous in the genome and span approximately 0.6 Mb near the top of zebrafish linkage group 7. One flanking region of the nitr gene complex shares conserved synteny with a region of mouse chromosome 7, which shares conserved synteny with human 19q13.3-q13.4 that encodes the leukocyte receptor cluster. Antibody-induced crosslinking of Nitrs that have been introduced into a human natural killer cell line inhibits the phosphorylation of mitogen-activated protein kinase that is triggered by natural killer-sensitive tumor target cells. Nitrs likely represent intermediates in the evolution of the leukocyte receptor cluster.
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Affiliation(s)
- J A Yoder
- Department of Pediatrics, University of South Florida, Children's Research Institute, St. Petersburg, FL 33701, USA
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