Specific Recognition of Protein Carboxy-Terminal Sequences by Natural IgM Antibodies in Normal Serum

• DOI: 10.1006/mthe.2001.0340
• Publication Date: 2002-09-18T19:46:30Z
• Authors: Alex V. Sokoloff; Ildiko Bock; Guofeng Zhang; Sara Hoffman; James Dama; James J. Ludtke; Anne M. Cooke; Jon A. Wolff
• Keywords: Pharmacology; 0301 basic medicine; Genetic Vectors; Enzyme-Linked Immunosorbent Assay; Ligands; Peptide Fragments; Rats; 3. Good health; Antigen-Antibody Reactions; Rats, Sprague-Dawley; Epitopes; 03 medical and health sciences; 0302 clinical medicine; Immunoglobulin M; Antibody Specificity; Peptide Library; Bacteriophage T7; Drug Discovery; Antibody Formation; Genetics; Escherichia coli; Molecular Medicine; Animals; Molecular Biology

Our previous study indicated that normal serum contains complement-fixing natural IgM antibodies reacting with a large variety of randomly generated protein carboxy-termini. Here we show that the "carboxy-terminal" IgM (C-IgM) antibodies specifically react with short peptide sequences located immediately at the protein carboxy-terminus. The specificity of C-IgM-peptide interactions is tentatively defined by three to four amino acid residues. All carboxy-terminal peptides in a large peptide library apparently react with C-IgM antibodies. Immobilized synthetic peptides also react with C-IgM antibodies. No interaction of C-IgM antibodies with internal peptide sequences has been observed. C-IgM antibodies are present in germ-free and in athymic adult rats and are absent in newborn rats. The natural ubiquity of protein carboxy-termini in biological structures suggests that C-IgM could play an important role in antigen clearance and presentation to the immune system. From a practical viewpoint, the recognition of carboxy-terminal peptides by complement-fixing C-IgM antibodies has profound implications for the use of peptide- and protein-derivatized delivery vehicles and artificial materials.