A Human Leucocyte Antigen‐DR1 Transgene Confers Susceptibility to Experimental Allergic Encephalomyelitis Elicited by an Epitope of Myelin Basic Protein
Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA‐restricted presentation of T‐cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of...
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| Veröffentlicht in: | Scandinavian journal of immunology 2003-08, Vol.58 (2), p.188-194 |
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| creator | Sireci, G. Dieli, F. Caccamo, N. Barera, A. Carta, P. Di Sano, C. Meraviglia, S. Bonanno, C. T. Salerno, A. |
| description | Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA‐restricted presentation of T‐cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA‐DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13–33, 87–106 and 139–154 bound by HLA‐DR1. We report here that HLA‐DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13–33 epitope induced a strong T helper 1 (Th1) response accompanied by high T‐cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139–154) or no disease (87–106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE. |
| doi_str_mv | 10.1046/j.1365-3083.2003.01296.x |
| format | Article |
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T. ; Salerno, A.</creator><creatorcontrib>Sireci, G. ; Dieli, F. ; Caccamo, N. ; Barera, A. ; Carta, P. ; Di Sano, C. ; Meraviglia, S. ; Bonanno, C. T. ; Salerno, A.</creatorcontrib><description>Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA‐restricted presentation of T‐cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA‐DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13–33, 87–106 and 139–154 bound by HLA‐DR1. We report here that HLA‐DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13–33 epitope induced a strong T helper 1 (Th1) response accompanied by high T‐cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139–154) or no disease (87–106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.</description><identifier>ISSN: 0300-9475</identifier><identifier>EISSN: 1365-3083</identifier><identifier>DOI: 10.1046/j.1365-3083.2003.01296.x</identifier><identifier>PMID: 12869140</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Amino Acid Sequence ; Animals ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental - genetics ; Encephalomyelitis, Autoimmune, Experimental - immunology ; Epitopes, T-Lymphocyte - immunology ; Female ; Genetic Predisposition to Disease ; histocompatibility antigen HLA ; HLA-DR1 Antigen - genetics ; HLA-DR1 Antigen - immunology ; Humans ; Lymph Nodes - immunology ; Male ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Multiple Sclerosis - genetics ; Multiple Sclerosis - immunology ; Myelin Basic Protein - genetics ; Myelin Basic Protein - immunology ; Peptide Fragments - immunology</subject><ispartof>Scandinavian journal of immunology, 2003-08, Vol.58 (2), p.188-194</ispartof><rights>Copyright Blackwell Scientific Publications Ltd. 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T.</creatorcontrib><creatorcontrib>Salerno, A.</creatorcontrib><title>A Human Leucocyte Antigen‐DR1 Transgene Confers Susceptibility to Experimental Allergic Encephalomyelitis Elicited by an Epitope of Myelin Basic Protein</title><title>Scandinavian journal of immunology</title><addtitle>Scand J Immunol</addtitle><description>Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA‐restricted presentation of T‐cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA‐DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13–33, 87–106 and 139–154 bound by HLA‐DR1. We report here that HLA‐DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13–33 epitope induced a strong T helper 1 (Th1) response accompanied by high T‐cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139–154) or no disease (87–106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>Encephalomyelitis, Autoimmune, Experimental - genetics</subject><subject>Encephalomyelitis, Autoimmune, Experimental - immunology</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>histocompatibility antigen HLA</subject><subject>HLA-DR1 Antigen - genetics</subject><subject>HLA-DR1 Antigen - immunology</subject><subject>Humans</subject><subject>Lymph Nodes - immunology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Multiple Sclerosis - genetics</subject><subject>Multiple Sclerosis - immunology</subject><subject>Myelin Basic Protein - genetics</subject><subject>Myelin Basic Protein - immunology</subject><subject>Peptide Fragments - immunology</subject><issn>0300-9475</issn><issn>1365-3083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUGP1CAUxxujcWdXv4IhHry1QmlpOXgYx-quGaNx1zOh9HVlwkCFNk5v-xE8-_H8JFJnookXPQHh93-8xy9JEMEZwQV7vssIZWVKcU2zHGOaYZJzlh3uJavfF_eTFaYYp7yoyrPkPIQdxoTmFX2YnJG8ZpwUeJV8X6PLaS8t2sKknJpHQGs76luwP-6-vfpI0I2XNsQjoI2zPfiArqegYBh1q40eZzQ61BwG8HoPdpQGrY0Bf6sVamzEPkvj9jNEUgfUGK30CB1qZxSfbAY9ugGQ69G7BbHopQwx-MG7EbR9lDzopQnw-LReJJ9eNzeby3T7_s3VZr1NVUk5SxXru1YWLeYlrQpWqLLoVS4ZLQjJOy5VxfKqozW0LFcgZa1wVyqeg6wkrSmhF8mzY93Buy8ThFHsdZzQGGnBTUFUtOCkrP4Nkjq2gFkdwad_gTs3eRuHEITXhFexswjVR0h5F4KHXgzxD6WfBcFisSx2YpEpFplisSx-WRaHGH1yqj-1e-j-BE9aI_DiCHzVBub_Liyu314tO_oTt4O4UA</recordid><startdate>200308</startdate><enddate>200308</enddate><creator>Sireci, G.</creator><creator>Dieli, F.</creator><creator>Caccamo, N.</creator><creator>Barera, A.</creator><creator>Carta, P.</creator><creator>Di Sano, C.</creator><creator>Meraviglia, S.</creator><creator>Bonanno, C. T.</creator><creator>Salerno, A.</creator><general>Blackwell Science Ltd</general><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>200308</creationdate><title>A Human Leucocyte Antigen‐DR1 Transgene Confers Susceptibility to Experimental Allergic Encephalomyelitis Elicited by an Epitope of Myelin Basic Protein</title><author>Sireci, G. ; Dieli, F. ; Caccamo, N. ; Barera, A. ; Carta, P. ; Di Sano, C. ; Meraviglia, S. ; Bonanno, C. 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T.</au><au>Salerno, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Human Leucocyte Antigen‐DR1 Transgene Confers Susceptibility to Experimental Allergic Encephalomyelitis Elicited by an Epitope of Myelin Basic Protein</atitle><jtitle>Scandinavian journal of immunology</jtitle><addtitle>Scand J Immunol</addtitle><date>2003-08</date><risdate>2003</risdate><volume>58</volume><issue>2</issue><spage>188</spage><epage>194</epage><pages>188-194</pages><issn>0300-9475</issn><eissn>1365-3083</eissn><abstract>Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA‐restricted presentation of T‐cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA‐DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13–33, 87–106 and 139–154 bound by HLA‐DR1. We report here that HLA‐DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13–33 epitope induced a strong T helper 1 (Th1) response accompanied by high T‐cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139–154) or no disease (87–106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12869140</pmid><doi>10.1046/j.1365-3083.2003.01296.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Animals Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental - genetics Encephalomyelitis, Autoimmune, Experimental - immunology Epitopes, T-Lymphocyte - immunology Female Genetic Predisposition to Disease histocompatibility antigen HLA HLA-DR1 Antigen - genetics HLA-DR1 Antigen - immunology Humans Lymph Nodes - immunology Male Mice Mice, Transgenic Molecular Sequence Data Multiple Sclerosis - genetics Multiple Sclerosis - immunology Myelin Basic Protein - genetics Myelin Basic Protein - immunology Peptide Fragments - immunology |
| title | A Human Leucocyte Antigen‐DR1 Transgene Confers Susceptibility to Experimental Allergic Encephalomyelitis Elicited by an Epitope of Myelin Basic Protein |
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