K. Bauer, M. Janitz, L. Reiners-Schramm, A. Mühlethaler-Mottet, Mark Rosowski, R. Lauster, J. Agnholt, K. Kaltoft, K. W. Eriksen, M. Nielsen, K. Kaltoft, A. Svejgaard, M. Nissen, C. Röpke, N. Ødum, Christèle Martinez-Jean, G. Folch, M. Lefranc, P. Ramsland, A. Kaushik, J. Marchalonis, A. Edmundson, A. Császár, J. Duba, B. Melegh, J. Kramer, C. Szalai, Z. Prohászka, I. Karádi, M. Kovács, K. Méhes, L. Romics, G. Füst, H. Takeshita, T. Yasuda, E. Nakazato, T. Nakajima, Shinjiro Mori, K. Mogi, Y. Kaneko, R. Iida, K. Kishi
{"title":"Subject Index Vol. 18, 2001","authors":"K. Bauer, M. Janitz, L. Reiners-Schramm, A. Mühlethaler-Mottet, Mark Rosowski, R. Lauster, J. Agnholt, K. Kaltoft, K. W. Eriksen, M. Nielsen, K. Kaltoft, A. Svejgaard, M. Nissen, C. Röpke, N. Ødum, Christèle Martinez-Jean, G. Folch, M. Lefranc, P. Ramsland, A. Kaushik, J. Marchalonis, A. Edmundson, A. Császár, J. Duba, B. Melegh, J. Kramer, C. Szalai, Z. Prohászka, I. Karádi, M. Kovács, K. Méhes, L. Romics, G. Füst, H. Takeshita, T. Yasuda, E. Nakazato, T. Nakajima, Shinjiro Mori, K. Mogi, Y. Kaneko, R. Iida, K. Kishi","doi":"10.1159/000049206","DOIUrl":"https://doi.org/10.1159/000049206","url":null,"abstract":"","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64622442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
‘Nomenclature and overview of the mouse (Mus musculus and Mus sp.) immunoglobulin kappa (IGK) Genes’, the 19th report of the ‘IMGT Locus in Focus’ section, provides the first complete list of all the mouse (M. musculus) IGK genes. The mouse (M. musculus) locus spans 3,200 kb. The total number of mouse (M. musculus) IGK genes per haploid genome is 164 (174 if the orphons are included). The functional genomic repertoire comprises 93 IGKV belonging to 18 subgroups, 5 IGKJ and 1 IGKC gene. IMGT gene names and definitions of the mouse (M. musculus) IGK genes on chromosome 6 and IGK orphons are provided with the gene functionality and the number of alleles, according to the concepts of IMGT-ONTOLOGY and to rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences. These tables and figures are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.
《小鼠(Mus musculus and Mus sp.)免疫球蛋白kappa (IGK)基因的命名法和概述》是“IMGT Locus in Focus”部分的第19篇报道，提供了所有小鼠(M. musculus) IGK基因的第一个完整列表。小鼠(m.m usculus)基因座跨度为3200 kb。每个单倍体基因组的IGK基因总数为164个(如果包括孤儿，则为174个)。功能基因组库包括93个IGKV，属于18个亚群，5个IGKJ和1个IGKC基因。根据IMGT- ontology的概念和IMGT科学图谱的规则，对小鼠(M. musculus) 6号染色体上的IGK基因和IGK孤儿的IMGT基因名称和定义提供了基因功能和等位基因数量，并提供了IMGT参考序列的加入号。这些表格和数据可在国际免疫遗传学数据库IMGT的IMGT Marie-Paule页面(http://imgt.cines.fr)获得，该数据库由法国蒙彼利埃第二大学的Marie-Paule Lefranc创建。
{"title":"Nomenclature and Overview of the Mouse (Mus musculus and Mus sp.) Immunoglobulin Kappa (IGK) Genes","authors":"Christèle Martinez-Jean, G. Folch, M. Lefranc","doi":"10.1159/000049204","DOIUrl":"https://doi.org/10.1159/000049204","url":null,"abstract":"‘Nomenclature and overview of the mouse (Mus musculus and Mus sp.) immunoglobulin kappa (IGK) Genes’, the 19th report of the ‘IMGT Locus in Focus’ section, provides the first complete list of all the mouse (M. musculus) IGK genes. The mouse (M. musculus) locus spans 3,200 kb. The total number of mouse (M. musculus) IGK genes per haploid genome is 164 (174 if the orphons are included). The functional genomic repertoire comprises 93 IGKV belonging to 18 subgroups, 5 IGKJ and 1 IGKC gene. IMGT gene names and definitions of the mouse (M. musculus) IGK genes on chromosome 6 and IGK orphons are provided with the gene functionality and the number of alleles, according to the concepts of IMGT-ONTOLOGY and to rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences. These tables and figures are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64622730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Cha, Saskia C.A. van Blockland, M. Versnel, F. Homo-Delarche, H. Nagashima, J. Brayer, A. Peck, M. Humphreys-Beher
Objectives: Salivary gland organogenesis was evaluated in NOD mice, an animal model for autoimmune exocrinopathy, to determine when disease onset is first present in the target tissues. Methods: Submandibular glands were removed for histological, immunohistochemical and biochemical evaluation from neonatal NOD and congenic strains as well as healthy control C57BL/6 mice. Results: Histomorphological analyses of neonatal submandibular glands, the primary target for autoimmune exocrinopathy at 1 day postpartum, revealed delayed morphological differentiation during organogenesis in autoimmune-susceptible NOD mice when compared to nonsusceptible C57BL/6 mice. Acinar cell proliferation was reduced, while expression of Fas, FasL and bcl-2 were increased. Acinar cell proliferation was reduced, while expression, of Fas, FasL and bcl-2 were increased. Throughout the preweaning period (21 days) submandibular glands from NOD and NOD congenic strains aberrantly expressed an increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. Substitution of two susceptibility alleles (Idd3 and Idd5) in NOD mice resulted in an hierarchical and additive reversal of delayed organogenesis, elevated MMP-9 activity, and aberrant expression of parotid secretory protein. Discussion: NOD-derived mice whose submandibular glands showed normal organogenesis did not progress to develop autoimmune exocrinopathy. Altered organogenesis of target tissue may therefore provide a cellular microenvironment capable of activating autoimmunity.
{"title":"Abnormal Organogenesis in Salivary Gland Development May Initiate Adult Onset of Autoimmune Exocrinopathy","authors":"S. Cha, Saskia C.A. van Blockland, M. Versnel, F. Homo-Delarche, H. Nagashima, J. Brayer, A. Peck, M. Humphreys-Beher","doi":"10.1159/000049194","DOIUrl":"https://doi.org/10.1159/000049194","url":null,"abstract":"Objectives: Salivary gland organogenesis was evaluated in NOD mice, an animal model for autoimmune exocrinopathy, to determine when disease onset is first present in the target tissues. Methods: Submandibular glands were removed for histological, immunohistochemical and biochemical evaluation from neonatal NOD and congenic strains as well as healthy control C57BL/6 mice. Results: Histomorphological analyses of neonatal submandibular glands, the primary target for autoimmune exocrinopathy at 1 day postpartum, revealed delayed morphological differentiation during organogenesis in autoimmune-susceptible NOD mice when compared to nonsusceptible C57BL/6 mice. Acinar cell proliferation was reduced, while expression of Fas, FasL and bcl-2 were increased. Acinar cell proliferation was reduced, while expression, of Fas, FasL and bcl-2 were increased. Throughout the preweaning period (21 days) submandibular glands from NOD and NOD congenic strains aberrantly expressed an increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. Substitution of two susceptibility alleles (Idd3 and Idd5) in NOD mice resulted in an hierarchical and additive reversal of delayed organogenesis, elevated MMP-9 activity, and aberrant expression of parotid secretory protein. Discussion: NOD-derived mice whose submandibular glands showed normal organogenesis did not progress to develop autoimmune exocrinopathy. Altered organogenesis of target tissue may therefore provide a cellular microenvironment capable of activating autoimmunity.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64621330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
‘Nomenclature of the Human Immunoglobulin Kappa (IGK) Genes’, the 17th report of the ‘IMGT Locus in Focus’ section, provides the first complete list of all the human IGK genes. In the most frequent haplotypes, the human IGK locus spans 1,820 kb and the IGKV genes are organized in two clusters separated by 800 kb. In those haplotypes where both the proximal and distal IGKV clusters are present, the total number of human IGK genes per haploid genome is 82 (107 genes if the orphons are included) of which 37–41 are functional. If only the proximal IGKV cluster is present, which is found in a rare haplotype, the total number of genes per haploid genome is 46 (71 genes if the orphons are included) of which 23–25 genes are functional. IMGT/HUGO gene names and definitions of the human IGK genes on chromosome 2p11.2, and IGK orphons on chromosomes 1, 2, 15, and 22 are provided with the gene functionality and the number of alleles according to the rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences, and the accession ID of the Genome Database GDB and NCBI LocusLink databases in which all the IMGT human IGK genes have been entered. The tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.
{"title":"Nomenclature of the Human Immunoglobulin Kappa (IGK) Genes","authors":"M. Lefranc","doi":"10.1159/000049195","DOIUrl":"https://doi.org/10.1159/000049195","url":null,"abstract":"‘Nomenclature of the Human Immunoglobulin Kappa (IGK) Genes’, the 17th report of the ‘IMGT Locus in Focus’ section, provides the first complete list of all the human IGK genes. In the most frequent haplotypes, the human IGK locus spans 1,820 kb and the IGKV genes are organized in two clusters separated by 800 kb. In those haplotypes where both the proximal and distal IGKV clusters are present, the total number of human IGK genes per haploid genome is 82 (107 genes if the orphons are included) of which 37–41 are functional. If only the proximal IGKV cluster is present, which is found in a rare haplotype, the total number of genes per haploid genome is 46 (71 genes if the orphons are included) of which 23–25 genes are functional. IMGT/HUGO gene names and definitions of the human IGK genes on chromosome 2p11.2, and IGK orphons on chromosomes 1, 2, 15, and 22 are provided with the gene functionality and the number of alleles according to the rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences, and the accession ID of the Genome Database GDB and NCBI LocusLink databases in which all the IMGT human IGK genes have been entered. The tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64621555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Schneider, K. Witzel-Schlömp, Constanze Steinhauer, B. Stradmann-Bellinghausen, C. Rittner
The fourth component of complement (C4) is coded for by two tandem-duplicated genes located in the class III region of the MHC of humans as well as a number of primates. A C4 gene size polymorphism giving rise to two gene variants of 16 and 22.3 kb length can be attributed to a complete endogenous retroviral insertion of 6.3 kb termed ERV-K(C4) in intron 9 of the long C4 genes. We developed a simple PCR-based screening assay to detect the presence of this insertion, and tested a number of unrelated animals from old world primate species. The presence of the ERV insertion in the orangutan, rhesus macaque and green monkey as well as its absence in gorillas and chimpanzees could be confirmed. In addition, the insertion was also detected in the baboon and the cynomolgus macaque whereas it was not found in a single gibbon. Among rhesus and cynomolgus macaques one individual was identified in each species only carrying short C4 genes demonstrating further structural heterogeneity in these species. Based on these findings we propose that the primigenial retroviral integration occurred prior to the radiation of old world primate species, and that both the long and the short forms of the C4 gene have existed side by side since then.
{"title":"Rapid Detection of the ERV-K(C4) Retroviral Insertion Reveals Further Structural Polymorphism of the Complement C4 Genes in Old World Primates","authors":"P. Schneider, K. Witzel-Schlömp, Constanze Steinhauer, B. Stradmann-Bellinghausen, C. Rittner","doi":"10.1159/000049192","DOIUrl":"https://doi.org/10.1159/000049192","url":null,"abstract":"The fourth component of complement (C4) is coded for by two tandem-duplicated genes located in the class III region of the MHC of humans as well as a number of primates. A C4 gene size polymorphism giving rise to two gene variants of 16 and 22.3 kb length can be attributed to a complete endogenous retroviral insertion of 6.3 kb termed ERV-K(C4) in intron 9 of the long C4 genes. We developed a simple PCR-based screening assay to detect the presence of this insertion, and tested a number of unrelated animals from old world primate species. The presence of the ERV insertion in the orangutan, rhesus macaque and green monkey as well as its absence in gorillas and chimpanzees could be confirmed. In addition, the insertion was also detected in the baboon and the cynomolgus macaque whereas it was not found in a single gibbon. Among rhesus and cynomolgus macaques one individual was identified in each species only carrying short C4 genes demonstrating further structural heterogeneity in these species. Based on these findings we propose that the primigenial retroviral integration occurred prior to the radiation of old world primate species, and that both the long and the short forms of the C4 gene have existed side by side since then.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64621477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We present evidence here that the proinflammatory cytokine, interleukin-1β (IL-1β) stimulates a significant increase in protein kinase C (PKC)-Ε and PKC-δ protein levels and increases PKC-Ε, but not PKC-δ, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1β induced protein synthesis of PKC-Ε (6-fold increase) by 7 h and had a biphasic effect on PKC-δ levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-Ε, but not PKC-δ levels, were induced after incubation of EL4 cells with IL-1β. The signalling mechanisms utilized by IL-1β to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1β-induced synthesis of PKC-Ε. However, the PI 3-kinase inhibitors had little effect on the IL-1β-induced synthesis of PKC-δ in these cells. Our results indicate that IL-1β induced both PKC-δ and PKC-Ε expression over different time periods. Furthermore, our evidence suggests that IL-1β induction of PKC-Ε, but not PKC-δ, may occur via the PI 3-kinase pathway.
{"title":"Interleukin-1β Induced Synthesis of Protein Kinase C-δ and Protein Kinase C-ε in EL4 Thymoma Cells: Possible Involvement of Phosphatidylinositol 3-Kinase","authors":"C. Varley, J. Royds, B. Brown, P. Dobson","doi":"10.1159/000049193","DOIUrl":"https://doi.org/10.1159/000049193","url":null,"abstract":"We present evidence here that the proinflammatory cytokine, interleukin-1β (IL-1β) stimulates a significant increase in protein kinase C (PKC)-Ε and PKC-δ protein levels and increases PKC-Ε, but not PKC-δ, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1β induced protein synthesis of PKC-Ε (6-fold increase) by 7 h and had a biphasic effect on PKC-δ levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-Ε, but not PKC-δ levels, were induced after incubation of EL4 cells with IL-1β. The signalling mechanisms utilized by IL-1β to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1β-induced synthesis of PKC-Ε. However, the PI 3-kinase inhibitors had little effect on the IL-1β-induced synthesis of PKC-δ in these cells. Our results indicate that IL-1β induced both PKC-δ and PKC-Ε expression over different time periods. Furthermore, our evidence suggests that IL-1β induction of PKC-Ε, but not PKC-δ, may occur via the PI 3-kinase pathway.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64621753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: The monoclonal IgG anti-double-stranded (ds) DNA antibody 32B9, obtained from a patient with systemic lupus erythematosus, was found to be encoded by somatically mutated immunoglobulin genes. We examined the input of several somatic mutations into antibody specificity and affinity. Methods: Five single-chain (sc) Fv fragments [variable domain of the heavy chain (VH)-linker-variable domain of the light chain (VL)] derived from 32B9 were constructed and expressed in Escherichia coli. These scFv fragments contained VH or VL fragments, differing in the somatic mutation pattern. The antigen binding features of the 32B9 IgG were compared with the corresponding scFv fragments, and the binding to DNA of all fragments was analyzed by ELISA. Binding constants to dsDNA were determined by surface plasmon resonance and ELISA. Results: The scFv 32B9 reflected the binding features of the 32B9 IgG. Independently of the somatic mutations, all scFv fragments bound to dsDNA in ELISA. The affinity data indicated that the mutations studied had only a marginal effect on affinity maturation of the 32B9. Discussion: We discuss the approach to constructing scFv fragments as a tool to study autoantibody maturation.
{"title":"Development of Single-Chain Fv Fragments from a Human Anti-Double-Stranded DNA Antibody to Study the Influence of Somatic Mutations on Antigen Binding","authors":"B. Kersten, B. Niemann, S. Jahn","doi":"10.1159/000049188","DOIUrl":"https://doi.org/10.1159/000049188","url":null,"abstract":"Objective: The monoclonal IgG anti-double-stranded (ds) DNA antibody 32B9, obtained from a patient with systemic lupus erythematosus, was found to be encoded by somatically mutated immunoglobulin genes. We examined the input of several somatic mutations into antibody specificity and affinity. Methods: Five single-chain (sc) Fv fragments [variable domain of the heavy chain (VH)-linker-variable domain of the light chain (VL)] derived from 32B9 were constructed and expressed in Escherichia coli. These scFv fragments contained VH or VL fragments, differing in the somatic mutation pattern. The antigen binding features of the 32B9 IgG were compared with the corresponding scFv fragments, and the binding to DNA of all fragments was analyzed by ELISA. Binding constants to dsDNA were determined by surface plasmon resonance and ELISA. Results: The scFv 32B9 reflected the binding features of the 32B9 IgG. Independently of the somatic mutations, all scFv fragments bound to dsDNA in ELISA. The affinity data indicated that the mutations studied had only a marginal effect on affinity maturation of the 32B9. Discussion: We discuss the approach to constructing scFv fragments as a tool to study autoantibody maturation.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64621204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Brockdorff, Haihua Gu, T. Mustelin, K. Kaltoft, C. Geisler, C. Röpke, N. Ødum
Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor β-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15-induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2 itself might be abnormally regulated by an Src family kinase.
{"title":"Gab2 Is Phosphorylated on Tyrosine upon Interleukin-2/Interleukin-15 Stimulation in Mycosis-fungoides-Derived Tumor T Cells and Associates Inducibly with SHP-2 and Stat5a","authors":"J. Brockdorff, Haihua Gu, T. Mustelin, K. Kaltoft, C. Geisler, C. Röpke, N. Ødum","doi":"10.1159/000049187","DOIUrl":"https://doi.org/10.1159/000049187","url":null,"abstract":"Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor β-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15-induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2 itself might be abnormally regulated by an Src family kinase.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64620986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Raux, D. Gilbert, P. Joly, P. Martel, J. Roujeau, C. Prost, M. Lefranc, F. Tron
Objective: To determine whether the immunoglobulin heavy chain genes contribute to the occurrence of bullous pemphigoid (BP), polymorphisms of both the immunoglobulin constant IGHC and variable IGHV groups were studied in 100 Caucasian BP patients and 143 ethnically matched healthy individuals. Methods: To analyze the restriction fragment length polymorphism (RFLP) of the IGHG constant locus, a genomic immunoglobulin gamma 3 probe which detects polymorphisms in the gamma constant genes was hybridized to BstEII- or BamHI/SacI-digested germline DNA, while IGHV3 subgroup polymorphism was analyzed by hybridizing a cloned VH3 probe to EcoRI-digested DNA. Results: No difference in the frequencies of the genotypes defined by the constant probe was observed between patients and controls. Analysis of the RFLP obtained with the VH3 probe showed that within the range of 4.5 and 1.5 kb, the observed band pattern was composed of 8 monomorphic and 7 polymorphic bands. Among the latter, 4 allowed to define 10 different restriction patterns. One pattern was shown to be significantly less frequent in patients than in controls. Conclusion: IGHV3 polymorphism might be a factor conferring susceptibility to BP.
{"title":"IGHV3-Associated Restriction Fragment Length Polymorphisms Confer Susceptibility to Bullous Pemphigoid","authors":"G. Raux, D. Gilbert, P. Joly, P. Martel, J. Roujeau, C. Prost, M. Lefranc, F. Tron","doi":"10.1159/000049183","DOIUrl":"https://doi.org/10.1159/000049183","url":null,"abstract":"Objective: To determine whether the immunoglobulin heavy chain genes contribute to the occurrence of bullous pemphigoid (BP), polymorphisms of both the immunoglobulin constant IGHC and variable IGHV groups were studied in 100 Caucasian BP patients and 143 ethnically matched healthy individuals. Methods: To analyze the restriction fragment length polymorphism (RFLP) of the IGHG constant locus, a genomic immunoglobulin gamma 3 probe which detects polymorphisms in the gamma constant genes was hybridized to BstEII- or BamHI/SacI-digested germline DNA, while IGHV3 subgroup polymorphism was analyzed by hybridizing a cloned VH3 probe to EcoRI-digested DNA. Results: No difference in the frequencies of the genotypes defined by the constant probe was observed between patients and controls. Analysis of the RFLP obtained with the VH3 probe showed that within the range of 4.5 and 1.5 kb, the observed band pattern was composed of 8 monomorphic and 7 polymorphic bands. Among the latter, 4 allowed to define 10 different restriction patterns. One pattern was shown to be significantly less frequent in patients than in controls. Conclusion: IGHV3 polymorphism might be a factor conferring susceptibility to BP.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64621133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Davies, D. Vannais, B. Fernie, A. B. Wilson, D. Gustafson, C. Willers, C. Waldren
We isolated a CD59 cDNA from a HeLa cell library which encoded a mutated form of CD59, having a single base substitution (G to T) that changed Arg55 to Met. Since this mutation occurred in the vicinity of the putative active site of CD59, we expressed the aberrant form of the protein in Chinese hamster ovary cells in order to test for effects upon function. We found that the mutation did not influence complement inhibitory activity of CD59. However, the epitopes recognised by the function-blocking CD59 monoclonal antibodies BRIC229 and YTH 53.1 were significantly affected. The G to T substitution caused loss of an Mnl I restriction site which permitted PCR-RFLP analysis. All of 52 human subjects studied, and our in-house HeLa cells, were homozygous for the normal CD59 sequence, indicating that the altered sequence was not due to normal variation in the general population. Therefore this mutation probably arose spontaneously in the HeLa cell line used to generate the commercially obtained cDNA library.
{"title":"An Aberrant Form of CD59 Derived from HeLa Cells","authors":"A. Davies, D. Vannais, B. Fernie, A. B. Wilson, D. Gustafson, C. Willers, C. Waldren","doi":"10.1159/000049185","DOIUrl":"https://doi.org/10.1159/000049185","url":null,"abstract":"We isolated a CD59 cDNA from a HeLa cell library which encoded a mutated form of CD59, having a single base substitution (G to T) that changed Arg55 to Met. Since this mutation occurred in the vicinity of the putative active site of CD59, we expressed the aberrant form of the protein in Chinese hamster ovary cells in order to test for effects upon function. We found that the mutation did not influence complement inhibitory activity of CD59. However, the epitopes recognised by the function-blocking CD59 monoclonal antibodies BRIC229 and YTH 53.1 were significantly affected. The G to T substitution caused loss of an Mnl I restriction site which permitted PCR-RFLP analysis. All of 52 human subjects studied, and our in-house HeLa cells, were homozygous for the normal CD59 sequence, indicating that the altered sequence was not due to normal variation in the general population. Therefore this mutation probably arose spontaneously in the HeLa cell line used to generate the commercially obtained cDNA library.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64620804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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