HLA DR and DQ interaction in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in HLA class II transgenic mice

Multiple sclerosis (MS) is shown to be associated with the HLA class II genes. The presence of strong linkage disequilibrium between HLA DR and DQ molecules in humans makes it difficult to identify the individual roles of HLA DR and HLA DQ molecule in MS pathogenesis. To address this problem, we use...

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Veröffentlicht in:Journal of neuroimmunology 2005-12, Vol.169 (1), p.1-12
Hauptverfasser: Khare, Meenakshi, Mangalam, Ashutosh, Rodriguez, Moses, David, Chella S.
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creator Khare, Meenakshi
Mangalam, Ashutosh
Rodriguez, Moses
David, Chella S.
description Multiple sclerosis (MS) is shown to be associated with the HLA class II genes. The presence of strong linkage disequilibrium between HLA DR and DQ molecules in humans makes it difficult to identify the individual roles of HLA DR and HLA DQ molecule in MS pathogenesis. To address this problem, we used HLA class II transgenic mice and the experimental autoimmune encephalitis (EAE) model. Administration of recombinant MOG (rMOG) induced severe inflammation and demyelination in the central nervous system (CNS) of HLA DRB1*1502 mice (60%), whereas no disease was observed in HLA DQB1*0601(0%) and mild disease was observed in DQB1*0302 mice (13%). Lymphocyte proliferation was blocked by anti HLA antibodies, confirming that the rMOG was functionally presented by the HLA molecules. Introduction of DQB1*0302 into DRB1*1502 mice resulted in the development of chronic progressive clinical disease characterized by severe inflammation and demyelination (90%) in response to immunization with rMOG, whereas mild disease was observed when DQB1*0601 was introduced in DRB1*1502 mice (30%). This would suggest that the presence of more than one susceptible allele, namely HLA DRB1*1502 and DQB1*0302 resulted in enhanced severity of disease in the DRB1*1502/DQB1*0302 mice, possibly due to the additional selection and expansion of potential autoreactive T cells. The use of defined single and double HLA transgenic mice may reveal the intricate interactions between class II molecules in human disease.
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The presence of strong linkage disequilibrium between HLA DR and DQ molecules in humans makes it difficult to identify the individual roles of HLA DR and HLA DQ molecule in MS pathogenesis. To address this problem, we used HLA class II transgenic mice and the experimental autoimmune encephalitis (EAE) model. Administration of recombinant MOG (rMOG) induced severe inflammation and demyelination in the central nervous system (CNS) of HLA DRB1*1502 mice (60%), whereas no disease was observed in HLA DQB1*0601(0%) and mild disease was observed in DQB1*0302 mice (13%). Lymphocyte proliferation was blocked by anti HLA antibodies, confirming that the rMOG was functionally presented by the HLA molecules. Introduction of DQB1*0302 into DRB1*1502 mice resulted in the development of chronic progressive clinical disease characterized by severe inflammation and demyelination (90%) in response to immunization with rMOG, whereas mild disease was observed when DQB1*0601 was introduced in DRB1*1502 mice (30%). This would suggest that the presence of more than one susceptible allele, namely HLA DRB1*1502 and DQB1*0302 resulted in enhanced severity of disease in the DRB1*1502/DQB1*0302 mice, possibly due to the additional selection and expansion of potential autoreactive T cells. 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Introduction of DQB1*0302 into DRB1*1502 mice resulted in the development of chronic progressive clinical disease characterized by severe inflammation and demyelination (90%) in response to immunization with rMOG, whereas mild disease was observed when DQB1*0601 was introduced in DRB1*1502 mice (30%). This would suggest that the presence of more than one susceptible allele, namely HLA DRB1*1502 and DQB1*0302 resulted in enhanced severity of disease in the DRB1*1502/DQB1*0302 mice, possibly due to the additional selection and expansion of potential autoreactive T cells. 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Mangalam, Ashutosh ; Rodriguez, Moses ; David, Chella S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-5a976a32161d30f5b2bdd6c3956590cf1b9b66d4e740adc27bafa1bc26b8aee93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Cell Proliferation</topic><topic>Cytokines - metabolism</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>EAE/MS</topic><topic>Encephalomyelitis, Autoimmune, Experimental - chemically induced</topic><topic>Encephalomyelitis, Autoimmune, Experimental - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay - methods</topic><topic>Flow Cytometry - methods</topic><topic>Genes, MHC Class II - genetics</topic><topic>HLA class II</topic><topic>HLA-DQ Antigens - metabolism</topic><topic>HLA-DR Antigens - metabolism</topic><topic>Interferon-gamma - metabolism</topic><topic>Interleukin-4 - metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Myelin oligodendrocyte glycoprotein</topic><topic>Myelin Proteins</topic><topic>Myelin-Associated Glycoprotein</topic><topic>Pathogenesis</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - pathology</topic><topic>Statistics, Nonparametric</topic><topic>T-Lymphocytes - physiology</topic><topic>Time Factors</topic><topic>Transgenic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khare, Meenakshi</creatorcontrib><creatorcontrib>Mangalam, Ashutosh</creatorcontrib><creatorcontrib>Rodriguez, Moses</creatorcontrib><creatorcontrib>David, Chella S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khare, Meenakshi</au><au>Mangalam, Ashutosh</au><au>Rodriguez, Moses</au><au>David, Chella S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HLA DR and DQ interaction in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in HLA class II transgenic mice</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>169</volume><issue>1</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>Multiple sclerosis (MS) is shown to be associated with the HLA class II genes. 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subjects Animals
Brain - metabolism
Brain - pathology
Cell Proliferation
Cytokines - metabolism
Dose-Response Relationship, Immunologic
EAE/MS
Encephalomyelitis, Autoimmune, Experimental - chemically induced
Encephalomyelitis, Autoimmune, Experimental - metabolism
Enzyme-Linked Immunosorbent Assay - methods
Flow Cytometry - methods
Genes, MHC Class II - genetics
HLA class II
HLA-DQ Antigens - metabolism
HLA-DR Antigens - metabolism
Interferon-gamma - metabolism
Interleukin-4 - metabolism
Mice
Mice, Transgenic
Myelin oligodendrocyte glycoprotein
Myelin Proteins
Myelin-Associated Glycoprotein
Pathogenesis
Spinal Cord - metabolism
Spinal Cord - pathology
Statistics, Nonparametric
T-Lymphocytes - physiology
Time Factors
Transgenic
title HLA DR and DQ interaction in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in HLA class II transgenic mice
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