Modulation of the immune response in multiple sclerosis: production of monoclonal antibodies specific to HLA/myelin basic protein.
Monoclonal Abs to the complex formed between human MHC class II molecules (DR7 and DRw11) and myelin basic protein (MBP) were produced. The specificity of these Abs was established by both FACS analysis and complement-mediated cytotoxicity of MBP- or OVA-pulsed human APC of the same or of different DR restriction. These Abs bound to and lysed only MBP-pulsed human APC of the same DR restriction (DR7 or DRw11) but not to APC of different DR restriction or pulsed with a different Ag (OVA). The physiologic role of these Abs was further investigated. They blocked the in vitro proliferative response to MBP-specific T cell clones isolated from multiple sclerosis patients in an antigen-specific and DR-restricted manner. However, the Abs did not affect the response of MBP-specific T cell clones of other DR restriction nor did they interfere with the response to other Ags (purified protein derivative or copolymer 1) presented on APC with the same DR restriction. These Abs may be useful for treating multiple sclerosis in which reactivity to MBP is implicated. Moreover, this approach may be extended to other autoantigens and their counterpart autoimmune diseases.
Puri
J
J
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Arnon
R
R
Gurevich
E
E
Teitelbaum
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D000918:Antibody Specificity; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001666:Binding Sites, Antibody; D002999:Clone Cells; D003165:Complement System Proteins / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D015809:HLA-DR7 Antigen / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D015809:HLA-DR7 Antigen; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D003165:Complement System Proteins