Sequence-specific binding of normal serum immunoglobulin M to exposed protein C-termini
Autor: | Marissa Puckett, Bryan Fetterly, James J. Ludtke, Alex V. Sokoloff |
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Rok vydání: | 2004 |
Předmět: |
Phage display
T7 phage Immunology Enzyme-Linked Immunosorbent Assay Antigen-Antibody Complex Complement receptor Binding Competitive Antigen-Antibody Reactions Antigen Antibody Specificity Peptide Library Bacteriophage T7 Humans Immunology and Allergy Complement Activation biology Original Articles biology.organism_classification Molecular biology Peptide Fragments J chain Complement system Immunoglobulin M biology.protein Antibody |
Zdroj: | Immunology. 112:237-249 |
ISSN: | 1365-2567 0019-2805 |
DOI: | 10.1111/j.1365-2567.2004.01868.x |
Popis: | Both the timely clearance of degraded endogenous structures and the presence of secreted natural immunoglobulin M (IgM) are needed to avoid autoimmunity. These requirements may be causally related provided that natural IgM preferentially reacts with degraded antigens and, by activating complement, mediates their non-inflammatory clearance through complement receptors. We have previously shown that normal serum IgM reacts in vivo and in vitro with virtually all randomly generated C-terminal peptides displayed on T7 phage. The resultant multivalent IgM-peptide complexes activate complement and are detected by a loss of phage infectivity. A striking feature of these reactions is that different C-terminal peptides ( approximately 3-4 amino acids) specifically react with different 'C-terminal' IgM (C-IgM) antibodies. This suggests that degraded supramolecular structures, expressing elevated levels of identical C-termini as a result of proteolysis, denaturation and abnormal exposure of repetitive protein constituents, may be preferential targets of C-IgM-mediated complement activation in the physiological environment. The specificity of C-IgM-peptide reactions is much higher than one would expect, assuming that normal serum IgM mostly comprises polyspecific natural antibodies. However, it is possible that polyspecific IgM is not adequately registered by our 'functional' phage-inactivation assays. In this study, we resolve the issue of C-IgM specificity by directly characterizing the binding reactivity of normal serum IgM with phage-displayed C-terminal peptides. |
Databáze: | OpenAIRE |
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