title: Characterization of a natural mouse monoclonal antibody recognizing epitopes shared by oxidized low-density lipoprotein and chaperonin 60 of Aggregatibacter actinomycetemcomitans.
abstract: Natural antibodies are predominantly antibodies of the IgM isotype present in the circulation of all vertebrates that have not been previously exposed to exogenous antigens. They are often directed against highly conserved epitopes and bind to ligands of varying chemical composition with low affinity. In this study we cloned and characterized a natural mouse monoclonal IgM antibody selected by binding to malondialdehyde acetaldehyde epitopes on low-density lipoprotein (LDL). Interestingly, the IgM antibody cross-reacted with Aggregatibacter actinomycetemcomitans (Aa) bacteria, a key pathogenic microbe in periodontitis reported to be associated with risk factor for atherosclerosis, thus being named as Aa_Mab. It is more intriguing that the binding molecule of Aa to Aa_Mab IgM was found to be Aa chaperonin 60 or HSP60, a member of heat-shock protein family, behaving not only as a chaperone for correct protein folding but also as a powerful virulence factor of the bacteria for inducing bone resorption and as a putative pathogenic factor in atherosclerosis. The findings will highlight the question of whether molecular mimicry between pathogen components and oxidized LDL could lead to atheroprotective immune activity, and also would be of great importance in potential application of immune response-based preventive and therapeutic strategies against atherosclerosis and periodontal disease.
authors.affiliation: Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland. chunguang.wang@oulu.fi.|Medical Research Center and Nordlab Oulu, University Hospital and University of Oulu, Oulu, Finland. chunguang.wang@oulu.fi.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland.|Medical Research Center and Nordlab Oulu, University Hospital and University of Oulu, Oulu, Finland.|Department of Neurology, Oulu University Hospital, Oulu, Finland.|Research Unit of Clinical Neuroscience and Medical Research Center Oulu, University of Oulu, Oulu, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Kankaanpää
authors.affiliation: Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland.|Medical Research Center and Nordlab Oulu, University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Kummu
authors.affiliation: Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland.|Medical Research Center and Nordlab Oulu, University Hospital and University of Oulu, Oulu, Finland.|Genome-scale Biology Research Program, University of Helsinki, Helsinki, Finland.
authors.forename: S Pauliina
authors.initials: SP
authors.lastname: Turunen
authors.affiliation: Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland.|Medical Research Center and Nordlab Oulu, University Hospital and University of Oulu, Oulu, Finland.|Research Unit of Oral Health Sciences, University of Oulu, Oulu, Finland.
authors.forename: Ramin
authors.initials: R
authors.lastname: Akhi
authors.affiliation: Protein Analysis Core Facility, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bergmann
authors.affiliation: Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Pussinen
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.|Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Remes
authors.affiliation: Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland.|Medical Research Center and Nordlab Oulu, University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Sohvi
authors.initials: S
authors.lastname: Hörkkö
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism*; D003001:Cloning, Molecular; D003429:Cross Reactions; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D051379:Mice; D018716:Molecular Mimicry; D016871:Pasteurellaceae Infections / Q000276:immunology*; D010518:Periodontitis / Q000276:immunology*; D017510:Protein Folding; D012306:Risk; D051127:Scavenger Receptors, Class E / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D018834:Chaperonin 60; D018985:Epitopes, B-Lymphocyte; D007075:Immunoglobulin M; D051127:Scavenger Receptors, Class E
keywords: Aggregatibacter actinomycetemcomitans; Chaperonin 60; Malondialdehyde acetaldehyde; Natural antibody; Oxidized low-density lipoprotein