title: Complement-coated antibody-transfer (CCAT); serum IgA1 antibodies intercept and transport C4 and C3 fragments and preserve IgG1 deployment (PGD).
abstract: In periodontal disease, IgG1 and IgA1 antibodies produced in situ deposit on antigens in the affected tissues. Thus, there is an interest in the effect of co-deposited IgA1 antibodies on complement activation by IgG1-immune complexes. In the present study, we first analyzed the effect of IgA1-immune complexes on complement using human IgA1 antibodies to dansyl (with dansylated human serum albumin serving as the immobilized antigen). It was observed that these IgA1-immune complexes when incubated for prolonged times with 33% human serum as a source of complement received C4b and C3b deposition. As C4b and C3b deposited on the IgA1 antibodies and on the antigenic surface, the complement-coated IgA1 antibodies departed. These fluid-phase complement-coated IgA1 antibodies were transferred to antigen-coated microtiter-ELISA plates, where they became bound to the antigens. Thus, the complement-coated IgA1 antibodies retained their antigen-binding function, especially as a proportion of their covalently bound C3b progressively degraded to iC3b and C3d. Genetically engineered carbohydrate-deficient mutant human IgA1 antibodies were used to assess the role of carbohydrate in accepting the C4b and C3b depositions, and these studies indicated that the carbohydrate on the Fc-region of IgA1 played a positive role. Another interesting finding generated by this study was that when IgA1 was co-deposited with IgG1 antibodies, and serum complement was added, the IgG1 antibodies tended to remain on the antigenic surface. The co-deposited IgA1 antibodies not only controlled (reduced) the rate of the consumption of the first component of complement (C1) and of classical complement pathway activation by IgG1-immune complexes (and therein reduced the rate of complement-mediated dissolution of the IgG1-immune complexes), but also the co-deposited IgA1 antibodies simultaneously intercepted/accepted C4b and C3b, then departed, as complement began to cover the antigenic surfaces. The process in which complement-coated IgA1 antibodies transferred to non-complement-coated antigens is termed complement-coated antibody-transfer/transport (CCAT). In this way, IgA1 antibodies extended the efficiency of the complement system by insuring the specific IgA1 antibody-mediated transport of the captured biologically active complement fragments to those antigens stimulating the IgA1 antibody response but not yet neutralized (completely coated) with complement. Simultaneously by impeding the rate of C1 consumption and by intercepting C4b and C3b, IgA1 antibodies slowed C4b and C3b deposition on the antigenic surface and on the co-deposited IgG1 antibodies. Thus, in the presence of ongoing complement activation, the deposition of serum IgA1 antibodies enabled the co-deposited IgG1 antibodies to better maintain their ability to interact with antigens. We termed this latter phenomenon, preservation of IgG antibody deployment (PGD). In summary, co-deposited IgA1 antibodies maximized the efficiency of the complement system, transported their covalently bound complement fragments to specific antigens and sustained the effective deployment of IgG1 antibodies directed to those same antigens.
authors.affiliation: Department of Stomatology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA. boacklrj@musc.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boackle
authors.forename: Quang L
authors.initials: QL
authors.lastname: Nguyen
authors.forename: Renata S
authors.initials: RS
authors.lastname: Leite
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.forename: Jana
authors.initials: J
authors.lastname: Vesely
mesh_terms: D000941:Antigens / Q000737:chemistry / Q000276:immunology; D001692:Biological Transport / Q000276:immunology; D015932:Complement C3c / Q000737:chemistry / Q000276:immunology*; D015933:Complement C3d / Q000737:chemistry / Q000276:immunology*; D015935:Complement C4b / Q000737:chemistry / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D007700:Kinetics; D010510:Periodontal Diseases / Q000276:immunology*
chemical_list: D000941:Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015932:Complement C3c; D015933:Complement C3d; D015935:Complement C4b