Visualization of myelin basic protein (mbp) t cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (hla)-dr2–mbp 85–99 complex (2000).

Content Provider	CiteSeerX
Author	Krogsgaard, Michelle Wucherpfennig, Kai W. Canella, Barbara Hansen, Bjarke E. Svejgaard, Arne Pyrdol, Jason Ditzel, Henrik Raine, Cedric Engberg, Jan Fugger, Lars
Abstract	Susceptibility to multiple sclerosis (MS) is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 haplotype, suggesting that major histocompatibility complex class II– restricted presentation of central nervous system–derived antigens is important in the disease process. Antibodies specific for defined HLA-DR2–peptide complexes may therefore be valuable tools for studying antigen presentation in MS. We have used phage display technology to select HLA-DR2–peptide-specific antibodies from HLA-DR2–transgenic mice immunized with HLA-DR2 molecules complexed with an immunodominant myelin basic protein (MBP) peptide (residues 85–99). Detailed characterization of one clone (MK16) demonstrated that both DR2 and the MBP peptide were required for recognition. Furthermore, MK16 labeled intra- and extracellular HLA-DR2–MBP peptide complexes when antigen-presenting cells (APCs) were pulsed with recombinant MBP. In addition, MK16 inhibited interleukin 2 secretion by two transfectants that expressed human MBP–specific T cell receptors. Analysis of the structural requirement for MK16 binding demonstrated that the two major HLA-DR2 anchor residues of MBP 85–99 and the COOH-terminal part of the peptide, in particular residues Val-
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Publisher Date	2000-01-01
Access Restriction	Open
Subject Keyword	Human Histocompatibility Leukocyte Antigen Dr2 Mbp Myelin Basic Protein Cell Epitope Multiple Sclerosis Lesion Monoclonal Antibody Specific Dr2 Haplotype Defined Hla-dr2 Peptide Complex Antigen Presentation Immunodominant Myelin Basic Protein Major Histocompatibility Complex Class Ii Particular Residue Antigen-presenting Cell Central Nervous System Valuable Tool Human Mbp Specific Cell Receptor Structural Requirement Extracellular Hla-dr2 Mbp Peptide Complex Mk16 Binding Major Hla-dr2 Anchor Residue Hla-dr2 Transgenic Mouse Cooh-terminal Part Hla-dr2 Molecule Recombinant Mbp Disease Process Hla-dr2 Peptide-specific Antibody Detailed Characterization Phage Display Technology Mbp Peptide
Content Type	Text