Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse
Natural antibodies that react with galactose-alpha(1,3)galactose [galalpha(1,3)gal] carbohydrate epitopes exist in humans and Old World primates because of the inactivation of the alpha1,3-galactosyltransferase (alpha1,3GT) gene in these species and the subsequent production of antibodies to environ...
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| Veröffentlicht in: | Transplantation 2001-07, Vol.72 (1), p.147-155 |
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| creator | Nozawa, S Xing, P X Wu, G D Gochi, E Kearns-Jonker, M Swensson, J Starnes, V A Sandrin, M S McKenzie, I F Cramer, D V |
| description | Natural antibodies that react with galactose-alpha(1,3)galactose [galalpha(1,3)gal] carbohydrate epitopes exist in humans and Old World primates because of the inactivation of the alpha1,3-galactosyltransferase (alpha1,3GT) gene in these species and the subsequent production of antibodies to environmental microbes that express the galalpha(1,3)gal antigen. The Gal knockout (Gal o/o) mouse, produced by homologous disruption of the alpha1,3GT gene, spontaneously makes anti-galalpha(1,3)gal antibodies and can be used to study the genetic control of humoral immune responses to this carbohydrate epitope.
Six hybridomas that produce monoclonal antibodies (mAbs) to galalpha(1,3)gal were generated in Gal o/o mice. The mAbs were tested to characterize the binding activity with flow cytometry using pig aortic endothelial cells and ELISA with galalpha(1,3)gal carbohydrates. The VH and VK genes of these hybridomas were cloned, sequenced, and analyzed.
The mAbs showed distinct patterns of antibody binding to galalpha(1,3)gal antigens. The VH genes that encode the mAb binding activity were restricted to a small number of genes expressed in their germline configuration. Four of six clones used closely related progeny of the same VH germline gene (VH441). Comparison of the mouse gene VH441 to the human gene IGHV3-11, a gene that encodes antibody activity to galalpha(1,3)gal in humans, demonstrates that these two genes share a nonrandom distribution of amino acids used at canonical binding sites within the variable regions (complimentary determining regions 1 and 2) of their immunoglobulin VH genes.
These results demonstrate the similarity of the Gal o/o mice and humans in their immune response to galalpha(1,3)gal epitopes. Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans. |
| doi_str_mv | 10.1097/00007890-200107150-00028 |
| format | Article |
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Six hybridomas that produce monoclonal antibodies (mAbs) to galalpha(1,3)gal were generated in Gal o/o mice. The mAbs were tested to characterize the binding activity with flow cytometry using pig aortic endothelial cells and ELISA with galalpha(1,3)gal carbohydrates. The VH and VK genes of these hybridomas were cloned, sequenced, and analyzed.
The mAbs showed distinct patterns of antibody binding to galalpha(1,3)gal antigens. The VH genes that encode the mAb binding activity were restricted to a small number of genes expressed in their germline configuration. Four of six clones used closely related progeny of the same VH germline gene (VH441). Comparison of the mouse gene VH441 to the human gene IGHV3-11, a gene that encodes antibody activity to galalpha(1,3)gal in humans, demonstrates that these two genes share a nonrandom distribution of amino acids used at canonical binding sites within the variable regions (complimentary determining regions 1 and 2) of their immunoglobulin VH genes.
These results demonstrate the similarity of the Gal o/o mice and humans in their immune response to galalpha(1,3)gal epitopes. Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans.</description><identifier>ISSN: 0041-1337</identifier><identifier>DOI: 10.1097/00007890-200107150-00028</identifier><identifier>PMID: 11468550</identifier><language>eng</language><publisher>United States</publisher><subject>a-1,3-Galactosyltransferase ; Amino Acid Sequence - genetics ; Animals ; Antibodies, Heterophile - genetics ; Antibodies, Heterophile - immunology ; Antigens, Heterophile - immunology ; Base Sequence - genetics ; carbohydrates ; Disaccharides - immunology ; Epitopes - genetics ; Galactosyltransferases - deficiency ; Galactosyltransferases - genetics ; Genes, Immunoglobulin - physiology ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Light Chains - genetics ; Immunoglobulin Variable Region - genetics ; Mice ; Mice, Knockout - genetics ; Molecular Sequence Data ; Swine</subject><ispartof>Transplantation, 2001-07, Vol.72 (1), p.147-155</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11468550$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nozawa, S</creatorcontrib><creatorcontrib>Xing, P X</creatorcontrib><creatorcontrib>Wu, G D</creatorcontrib><creatorcontrib>Gochi, E</creatorcontrib><creatorcontrib>Kearns-Jonker, M</creatorcontrib><creatorcontrib>Swensson, J</creatorcontrib><creatorcontrib>Starnes, V A</creatorcontrib><creatorcontrib>Sandrin, M S</creatorcontrib><creatorcontrib>McKenzie, I F</creatorcontrib><creatorcontrib>Cramer, D V</creatorcontrib><title>Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Natural antibodies that react with galactose-alpha(1,3)galactose [galalpha(1,3)gal] carbohydrate epitopes exist in humans and Old World primates because of the inactivation of the alpha1,3-galactosyltransferase (alpha1,3GT) gene in these species and the subsequent production of antibodies to environmental microbes that express the galalpha(1,3)gal antigen. The Gal knockout (Gal o/o) mouse, produced by homologous disruption of the alpha1,3GT gene, spontaneously makes anti-galalpha(1,3)gal antibodies and can be used to study the genetic control of humoral immune responses to this carbohydrate epitope.
Six hybridomas that produce monoclonal antibodies (mAbs) to galalpha(1,3)gal were generated in Gal o/o mice. The mAbs were tested to characterize the binding activity with flow cytometry using pig aortic endothelial cells and ELISA with galalpha(1,3)gal carbohydrates. The VH and VK genes of these hybridomas were cloned, sequenced, and analyzed.
The mAbs showed distinct patterns of antibody binding to galalpha(1,3)gal antigens. The VH genes that encode the mAb binding activity were restricted to a small number of genes expressed in their germline configuration. Four of six clones used closely related progeny of the same VH germline gene (VH441). Comparison of the mouse gene VH441 to the human gene IGHV3-11, a gene that encodes antibody activity to galalpha(1,3)gal in humans, demonstrates that these two genes share a nonrandom distribution of amino acids used at canonical binding sites within the variable regions (complimentary determining regions 1 and 2) of their immunoglobulin VH genes.
These results demonstrate the similarity of the Gal o/o mice and humans in their immune response to galalpha(1,3)gal epitopes. Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans.</description><subject>a-1,3-Galactosyltransferase</subject><subject>Amino Acid Sequence - genetics</subject><subject>Animals</subject><subject>Antibodies, Heterophile - genetics</subject><subject>Antibodies, Heterophile - immunology</subject><subject>Antigens, Heterophile - immunology</subject><subject>Base Sequence - genetics</subject><subject>carbohydrates</subject><subject>Disaccharides - immunology</subject><subject>Epitopes - genetics</subject><subject>Galactosyltransferases - deficiency</subject><subject>Galactosyltransferases - genetics</subject><subject>Genes, Immunoglobulin - physiology</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Light Chains - genetics</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Mice</subject><subject>Mice, Knockout - genetics</subject><subject>Molecular Sequence Data</subject><subject>Swine</subject><issn>0041-1337</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM9KxDAQxnNQ3HX1FSQnUbA6SbZNepTFf7DgRc9L2k67cdukNim4T-Brm-J6dhgY5vs-fgxDCGVwyyCXdxBLqhwSDsBAshSSqHB1ROYAS5YwIeSMnHr_EeVUSHlCZowtM5WmMCffq60edBlwMD6Y0lNXU9N1o3VN64qxNZY2aJGOXjc4mWGL9Aut0zaYwlV7WhhbGdvQ4Gij20S3_VZfsRtxHTca9NBgoFM4YjyNuAkwWTvryp0bA-3c6PGMHNe69Xh-mAvy_vjwtnpO1q9PL6v7ddLzJYREFxlkrBapqtIai5qLPM2RM65yjhlPRVVoKWMD5gIzxTIhSw6izgUHlEwsyOUvtx_c54g-bDrjS2xbbTHesZEMBKgM_g0yBUosMxGDF4fgWHRYbfrBdHrYb_5-LH4AJuF-SQ</recordid><startdate>20010715</startdate><enddate>20010715</enddate><creator>Nozawa, S</creator><creator>Xing, P X</creator><creator>Wu, G D</creator><creator>Gochi, E</creator><creator>Kearns-Jonker, M</creator><creator>Swensson, J</creator><creator>Starnes, V A</creator><creator>Sandrin, M S</creator><creator>McKenzie, I F</creator><creator>Cramer, D V</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20010715</creationdate><title>Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse</title><author>Nozawa, S ; Xing, P X ; Wu, G D ; Gochi, E ; Kearns-Jonker, M ; Swensson, J ; Starnes, V A ; Sandrin, M S ; McKenzie, I F ; Cramer, D V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p240t-ab6061f358d5febf23959e212892e6253dba77a770e93e681637c203f9320e713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>a-1,3-Galactosyltransferase</topic><topic>Amino Acid Sequence - genetics</topic><topic>Animals</topic><topic>Antibodies, Heterophile - genetics</topic><topic>Antibodies, Heterophile - immunology</topic><topic>Antigens, Heterophile - immunology</topic><topic>Base Sequence - genetics</topic><topic>carbohydrates</topic><topic>Disaccharides - immunology</topic><topic>Epitopes - genetics</topic><topic>Galactosyltransferases - deficiency</topic><topic>Galactosyltransferases - genetics</topic><topic>Genes, Immunoglobulin - physiology</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Light Chains - genetics</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Mice</topic><topic>Mice, Knockout - genetics</topic><topic>Molecular Sequence Data</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nozawa, S</creatorcontrib><creatorcontrib>Xing, P X</creatorcontrib><creatorcontrib>Wu, G D</creatorcontrib><creatorcontrib>Gochi, E</creatorcontrib><creatorcontrib>Kearns-Jonker, M</creatorcontrib><creatorcontrib>Swensson, J</creatorcontrib><creatorcontrib>Starnes, V A</creatorcontrib><creatorcontrib>Sandrin, M S</creatorcontrib><creatorcontrib>McKenzie, I F</creatorcontrib><creatorcontrib>Cramer, D V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nozawa, S</au><au>Xing, P X</au><au>Wu, G D</au><au>Gochi, E</au><au>Kearns-Jonker, M</au><au>Swensson, J</au><au>Starnes, V A</au><au>Sandrin, M S</au><au>McKenzie, I F</au><au>Cramer, D V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2001-07-15</date><risdate>2001</risdate><volume>72</volume><issue>1</issue><spage>147</spage><epage>155</epage><pages>147-155</pages><issn>0041-1337</issn><abstract>Natural antibodies that react with galactose-alpha(1,3)galactose [galalpha(1,3)gal] carbohydrate epitopes exist in humans and Old World primates because of the inactivation of the alpha1,3-galactosyltransferase (alpha1,3GT) gene in these species and the subsequent production of antibodies to environmental microbes that express the galalpha(1,3)gal antigen. The Gal knockout (Gal o/o) mouse, produced by homologous disruption of the alpha1,3GT gene, spontaneously makes anti-galalpha(1,3)gal antibodies and can be used to study the genetic control of humoral immune responses to this carbohydrate epitope.
Six hybridomas that produce monoclonal antibodies (mAbs) to galalpha(1,3)gal were generated in Gal o/o mice. The mAbs were tested to characterize the binding activity with flow cytometry using pig aortic endothelial cells and ELISA with galalpha(1,3)gal carbohydrates. The VH and VK genes of these hybridomas were cloned, sequenced, and analyzed.
The mAbs showed distinct patterns of antibody binding to galalpha(1,3)gal antigens. The VH genes that encode the mAb binding activity were restricted to a small number of genes expressed in their germline configuration. Four of six clones used closely related progeny of the same VH germline gene (VH441). Comparison of the mouse gene VH441 to the human gene IGHV3-11, a gene that encodes antibody activity to galalpha(1,3)gal in humans, demonstrates that these two genes share a nonrandom distribution of amino acids used at canonical binding sites within the variable regions (complimentary determining regions 1 and 2) of their immunoglobulin VH genes.
These results demonstrate the similarity of the Gal o/o mice and humans in their immune response to galalpha(1,3)gal epitopes. Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans.</abstract><cop>United States</cop><pmid>11468550</pmid><doi>10.1097/00007890-200107150-00028</doi><tpages>9</tpages></addata></record> |
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| subjects | a-1,3-Galactosyltransferase Amino Acid Sequence - genetics Animals Antibodies, Heterophile - genetics Antibodies, Heterophile - immunology Antigens, Heterophile - immunology Base Sequence - genetics carbohydrates Disaccharides - immunology Epitopes - genetics Galactosyltransferases - deficiency Galactosyltransferases - genetics Genes, Immunoglobulin - physiology Immunoglobulin Heavy Chains - genetics Immunoglobulin Light Chains - genetics Immunoglobulin Variable Region - genetics Mice Mice, Knockout - genetics Molecular Sequence Data Swine |
| title | Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse |
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