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

Abstract	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 DRB11502 mice (60%), whereas no disease was observed in HLA DQB10601(0%) and mild disease was observed in DQB10302 mice (13%). Lymphocyte proliferation was blocked by anti HLA antibodies, confirming that the rMOG was functionally presented by the HLA molecules. Introduction of DQB10302 into DRB11502 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 DQB10601 was introduced in DRB11502 mice (30%). This would suggest that the presence of more than one susceptible allele, namely HLA DRB11502 and DQB10302 resulted in enhanced severity of disease in the DRB11502/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.
Authors	Meenakshi Khare, Ashutosh Mangalam, Moses Rodriguez, Chella S David
Journal	Journal of neuroimmunology (J Neuroimmunol) Vol. 169 Issue 1-2 Pg. 1-12 (Dec 2005) ISSN: 0165-5728 [Print] Netherlands
PMID	16194572 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Cytokines HLA-DQ Antigens HLA-DR Antigens MOG protein, human Mog protein, mouse Myelin Proteins Myelin-Associated Glycoprotein Myelin-Oligodendrocyte Glycoprotein Interleukin-4 Interferon-gamma
Topics	Animals Brain (metabolism, pathology) Cell Proliferation Cytokines (metabolism) Dose-Response Relationship, Immunologic Encephalomyelitis, Autoimmune, Experimental (chemically induced, metabolism) Enzyme-Linked Immunosorbent Assay (methods) Flow Cytometry (methods) Genes, MHC Class II (genetics) HLA-DQ Antigens (metabolism) HLA-DR Antigens (metabolism) Interferon-gamma (metabolism) Interleukin-4 (metabolism) Mice Mice, Transgenic Myelin Proteins Myelin-Associated Glycoprotein Myelin-Oligodendrocyte Glycoprotein Spinal Cord (metabolism, pathology) Statistics, Nonparametric T-Lymphocytes (physiology) Time Factors

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