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T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor
Myasthenia gravis (MG) is an autoimmune disease caused by T cell‐dependent antibody‐mediated reduction of acetylcholine receptors (AChR) at the neuromuscular junction. Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions o...
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| Published in: | European journal of immunology 2002-07, Vol.32 (7), p.2055-2067 |
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| container_end_page | 2067 |
| container_issue | 7 |
| container_start_page | 2055 |
| container_title | European journal of immunology |
| container_volume | 32 |
| creator | Lobito, Adrian A. Yang, Bingzhi Lopes, Marcela F. Miagkov, Alexei Adams, Robert N. Palardy, Gregory R. Johnson, Michele M. McFarland, Hugh I. Recher, Michael Drachman, Daniel B. Lenardo, Michael J. |
| description | Myasthenia gravis (MG) is an autoimmune disease caused by T cell‐dependent antibody‐mediated reduction of acetylcholine receptors (AChR) at the neuromuscular junction. Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions of α and β T cell receptor (TCR) genes recognizing an immunodominant peptide containing amino acids 146–162 from the α subunit of TAChR presented in the context of I‐Ab to generate TCR‐transgenic mice. We found that the transgenic TCR was strongly positively selected and that transgenic T cells proliferated robustly to the immunodominant peptide and TAChR. Unexpectedly, there was a variable paucity of B cells in the blood and spleen from transgenic mice, which averaged about 16% of peripheral blood lymphocytes, compared to 55% in wild‐type B6 mice. Unselected transgenic mice immunized with TAChR exhibited weak anti‐TAChR antibody responses. However, transgenic mice selected to have relatively higher B cell numbers produced anti‐TAChR titers equal to B6 mice and a predominance of Th1‐induced antibody isotypes were observed in certain experiments. The incidence and severity of clinical disease was variable following immunizations. These mice should be useful for studying the pathogenesis and treatment of MG. |
| doi_str_mv | 10.1002/1521-4141(200207)32:7<2055::AID-IMMU2055>3.0.CO;2-Q |
| format | article |
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Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions of α and β T cell receptor (TCR) genes recognizing an immunodominant peptide containing amino acids 146–162 from the α subunit of TAChR presented in the context of I‐Ab to generate TCR‐transgenic mice. We found that the transgenic TCR was strongly positively selected and that transgenic T cells proliferated robustly to the immunodominant peptide and TAChR. Unexpectedly, there was a variable paucity of B cells in the blood and spleen from transgenic mice, which averaged about 16% of peripheral blood lymphocytes, compared to 55% in wild‐type B6 mice. Unselected transgenic mice immunized with TAChR exhibited weak anti‐TAChR antibody responses. However, transgenic mice selected to have relatively higher B cell numbers produced anti‐TAChR titers equal to B6 mice and a predominance of Th1‐induced antibody isotypes were observed in certain experiments. The incidence and severity of clinical disease was variable following immunizations. These mice should be useful for studying the pathogenesis and treatment of MG.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/1521-4141(200207)32:7<2055::AID-IMMU2055>3.0.CO;2-Q</identifier><identifier>PMID: 12115627</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag GmbH</publisher><subject>Amino Acid Sequence ; Animals ; Antibody ; B cell ; B-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - immunology ; Cell Division ; Epitopes, T-Lymphocyte - immunology ; Experimental autoimmune myasthenia gravis ; Gene Expression ; Immunodominant Epitopes - immunology ; Lymphocyte Count ; Lymphocytic choriomeningitis virus - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Sequence Data ; Myasthenia gravis ; Myasthenia Gravis, Autoimmune, Experimental - immunology ; Receptors, Antigen, T-Cell, alpha-beta - genetics ; Receptors, Antigen, T-Cell, alpha-beta - immunology ; Receptors, Cholinergic - immunology ; TCR transgenic ; Torpedo ; Vesicular stomatitis Indiana virus - immunology</subject><ispartof>European journal of immunology, 2002-07, Vol.32 (7), p.2055-2067</ispartof><rights>WILEY‐VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F1521-4141%28200207%2932%3A7%3C2055%3A%3AAID-IMMU2055%3E3.0.CO%3B2-Q$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F1521-4141%28200207%2932%3A7%3C2055%3A%3AAID-IMMU2055%3E3.0.CO%3B2-Q$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12115627$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lobito, Adrian A.</creatorcontrib><creatorcontrib>Yang, Bingzhi</creatorcontrib><creatorcontrib>Lopes, Marcela F.</creatorcontrib><creatorcontrib>Miagkov, Alexei</creatorcontrib><creatorcontrib>Adams, Robert N.</creatorcontrib><creatorcontrib>Palardy, Gregory R.</creatorcontrib><creatorcontrib>Johnson, Michele M.</creatorcontrib><creatorcontrib>McFarland, Hugh I.</creatorcontrib><creatorcontrib>Recher, Michael</creatorcontrib><creatorcontrib>Drachman, Daniel B.</creatorcontrib><creatorcontrib>Lenardo, Michael J.</creatorcontrib><title>T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>Myasthenia gravis (MG) is an autoimmune disease caused by T cell‐dependent antibody‐mediated reduction of acetylcholine receptors (AChR) at the neuromuscular junction. Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions of α and β T cell receptor (TCR) genes recognizing an immunodominant peptide containing amino acids 146–162 from the α subunit of TAChR presented in the context of I‐Ab to generate TCR‐transgenic mice. We found that the transgenic TCR was strongly positively selected and that transgenic T cells proliferated robustly to the immunodominant peptide and TAChR. Unexpectedly, there was a variable paucity of B cells in the blood and spleen from transgenic mice, which averaged about 16% of peripheral blood lymphocytes, compared to 55% in wild‐type B6 mice. Unselected transgenic mice immunized with TAChR exhibited weak anti‐TAChR antibody responses. However, transgenic mice selected to have relatively higher B cell numbers produced anti‐TAChR titers equal to B6 mice and a predominance of Th1‐induced antibody isotypes were observed in certain experiments. The incidence and severity of clinical disease was variable following immunizations. These mice should be useful for studying the pathogenesis and treatment of MG.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibody</subject><subject>B cell</subject><subject>B-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Division</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Experimental autoimmune myasthenia gravis</subject><subject>Gene Expression</subject><subject>Immunodominant Epitopes - immunology</subject><subject>Lymphocyte Count</subject><subject>Lymphocytic choriomeningitis virus - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Myasthenia gravis</subject><subject>Myasthenia Gravis, Autoimmune, Experimental - immunology</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - genetics</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - immunology</subject><subject>Receptors, Cholinergic - immunology</subject><subject>TCR transgenic</subject><subject>Torpedo</subject><subject>Vesicular stomatitis Indiana virus - immunology</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNqVkV1r2zAUhsVYWdNsf2HoamwXzo4-HMtpGZTso4GWUJbC7oQiH6UatuXJDmv262cvWXo1yq7E0Xn1PoiHkHMGEwbA37OUs0Qyyd7yfoTsneCz7IJDms5ml4uPyeLm5m6YPogJTObLc57cPiOj46vnZATAZMJzBafkrG2_A0A-TfMX5JRxxtIpz0bkYUUtliWNaLHpQqRdNHW7wdpbWnmLwyJsav_L1xva3SP1VbWtQxEqX5u6o9j4LjRIg_uzXYXYYBGoNaV3IfYthhqL3a6096H0NR5BL8mJM2WLrw7nmNx9_rSaXyXXyy-L-eV1YiWINFkr5QCU4oJPrWOpQ-e4U9KgyXmOa7BMKOvytYRcSMkUlwoyZ4oMeQHCiTF5s-9tYvixxbbTlW-HL5saw7bVGVO5kpA9GWQqzVLRU8bk6z5oY2jbiE430Vcm7jQDPZjTgwM9ONB7c1pwnenBlda9Of3XnBYa9Hypub7tW18f8Nt1hcVj50FVH_i2D_z0Je7-h_kP5PFO_AaNhbTk</recordid><startdate>200207</startdate><enddate>200207</enddate><creator>Lobito, Adrian A.</creator><creator>Yang, Bingzhi</creator><creator>Lopes, Marcela F.</creator><creator>Miagkov, Alexei</creator><creator>Adams, Robert N.</creator><creator>Palardy, Gregory R.</creator><creator>Johnson, Michele M.</creator><creator>McFarland, Hugh I.</creator><creator>Recher, Michael</creator><creator>Drachman, Daniel B.</creator><creator>Lenardo, Michael J.</creator><general>WILEY‐VCH Verlag GmbH</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200207</creationdate><title>T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor</title><author>Lobito, Adrian A. ; Yang, Bingzhi ; Lopes, Marcela F. ; Miagkov, Alexei ; Adams, Robert N. ; Palardy, Gregory R. ; Johnson, Michele M. ; McFarland, Hugh I. ; Recher, Michael ; Drachman, Daniel B. ; Lenardo, Michael J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4035-b88f00882326cf15feff2f84aea929eb0c138cf9b4093441824807fad7e2d03f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibody</topic><topic>B cell</topic><topic>B-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Division</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Experimental autoimmune myasthenia gravis</topic><topic>Gene Expression</topic><topic>Immunodominant Epitopes - immunology</topic><topic>Lymphocyte Count</topic><topic>Lymphocytic choriomeningitis virus - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Molecular Sequence Data</topic><topic>Myasthenia gravis</topic><topic>Myasthenia Gravis, Autoimmune, Experimental - immunology</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - genetics</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - immunology</topic><topic>Receptors, Cholinergic - immunology</topic><topic>TCR transgenic</topic><topic>Torpedo</topic><topic>Vesicular stomatitis Indiana virus - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lobito, Adrian A.</creatorcontrib><creatorcontrib>Yang, Bingzhi</creatorcontrib><creatorcontrib>Lopes, Marcela F.</creatorcontrib><creatorcontrib>Miagkov, Alexei</creatorcontrib><creatorcontrib>Adams, Robert N.</creatorcontrib><creatorcontrib>Palardy, Gregory R.</creatorcontrib><creatorcontrib>Johnson, Michele M.</creatorcontrib><creatorcontrib>McFarland, Hugh I.</creatorcontrib><creatorcontrib>Recher, Michael</creatorcontrib><creatorcontrib>Drachman, Daniel B.</creatorcontrib><creatorcontrib>Lenardo, Michael J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lobito, Adrian A.</au><au>Yang, Bingzhi</au><au>Lopes, Marcela F.</au><au>Miagkov, Alexei</au><au>Adams, Robert N.</au><au>Palardy, Gregory R.</au><au>Johnson, Michele M.</au><au>McFarland, Hugh I.</au><au>Recher, Michael</au><au>Drachman, Daniel B.</au><au>Lenardo, Michael J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2002-07</date><risdate>2002</risdate><volume>32</volume><issue>7</issue><spage>2055</spage><epage>2067</epage><pages>2055-2067</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><notes>A.A.L., B.Z., M.F.L., A.M., D.B.D. and M.J.L. contributed equally to this work.</notes><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>Myasthenia gravis (MG) is an autoimmune disease caused by T cell‐dependent antibody‐mediated reduction of acetylcholine receptors (AChR) at the neuromuscular junction. Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions of α and β T cell receptor (TCR) genes recognizing an immunodominant peptide containing amino acids 146–162 from the α subunit of TAChR presented in the context of I‐Ab to generate TCR‐transgenic mice. We found that the transgenic TCR was strongly positively selected and that transgenic T cells proliferated robustly to the immunodominant peptide and TAChR. Unexpectedly, there was a variable paucity of B cells in the blood and spleen from transgenic mice, which averaged about 16% of peripheral blood lymphocytes, compared to 55% in wild‐type B6 mice. Unselected transgenic mice immunized with TAChR exhibited weak anti‐TAChR antibody responses. However, transgenic mice selected to have relatively higher B cell numbers produced anti‐TAChR titers equal to B6 mice and a predominance of Th1‐induced antibody isotypes were observed in certain experiments. The incidence and severity of clinical disease was variable following immunizations. These mice should be useful for studying the pathogenesis and treatment of MG.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag GmbH</pub><pmid>12115627</pmid><doi>10.1002/1521-4141(200207)32:7<2055::AID-IMMU2055>3.0.CO;2-Q</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Animals Antibody B cell B-Lymphocytes - immunology CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology Cell Division Epitopes, T-Lymphocyte - immunology Experimental autoimmune myasthenia gravis Gene Expression Immunodominant Epitopes - immunology Lymphocyte Count Lymphocytic choriomeningitis virus - immunology Mice Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Myasthenia gravis Myasthenia Gravis, Autoimmune, Experimental - immunology Receptors, Antigen, T-Cell, alpha-beta - genetics Receptors, Antigen, T-Cell, alpha-beta - immunology Receptors, Cholinergic - immunology TCR transgenic Torpedo Vesicular stomatitis Indiana virus - immunology |
| title | T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor |
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