Molecular Immunologic Strategies to Identify Antigens and B-Cell Responses Unique to Multiple Sclerosis
| Autor: | R. Anthony Williamson, Bette K. Kleinschmidt-DeMasters, Dennis R. Burton, Gregory P. Owens, Omar Ghausi, Mark P. Burgoon, Donald H. Gilden |
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| Rok vydání: | 2001 |
| Předmět: |
DNA
Complementary Multiple Sclerosis Antibody Affinity DNA Recombinant Immunoglobulins Antibodies Viral Immunoglobulin G Epitope Epitopes Immune system Immunologic Technique Arts and Humanities (miscellaneous) Antigen Antigens CD Peptide Library medicine Humans RNA Messenger Cloning Molecular B cell Gene Library B-Lymphocytes Polymorphism Genetic biology Multiple sclerosis Antibodies Monoclonal Brain medicine.disease Virology medicine.anatomical_structure Chronic Disease Immunology Disease Progression biology.protein Feasibility Studies Neurology (clinical) Antibody |
| Zdroj: | Archives of Neurology. 58 |
| ISSN: | 0003-9942 |
| DOI: | 10.1001/archneur.58.1.43 |
| Popis: | Identification of the causative agent of multiple sclerosis (MS) has long eluded investigators and has become the "Holy Grail" of researchers in the field. The immune response in cerebrospinal fluid of patients with MS, indicated by an increased IgG level and the presence of specific oligoclonal bands after electrophoresis, strongly parallels that found in various infectious diseases of the central nervous system. To understand the nature of B-lymphocyte activation in MS, 4 laboratories studied the antigen-binding regions of antibodies found in MS brain demyelinative plaques and cerebrospinal fluid. Each analysis revealed (1) limited germline expression, results not expected for a random bystander response; (2) features consistent with a specific antigen-targeted process; and (3) the clonal expansion of populations of B lymphocytes in MS. The screening of libraries expressing protein products derived from chronic MS plaque messenger RNA with antibodies purified from plaques, cerebrospinal fluid, or serum of patients with MS has thus far not revealed the antigenic target(s) of the MS antibody response. Because putative MS antigens could be in low abundance, the screening of large libraries of random peptides expressed on phage surfaces might offer an alternative approach to identify peptide sequences recognized by MS antibodies. New sophisticated molecular immunologic techniques described herein should enhance our ability to identify putative antigen(s) targets in MS. |
| Databáze: | OpenAIRE |
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