B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice

BACKGROUND: HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65(336-439) instigates autoimmunity, suggesting that pp65(336-439) contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65(422-439) for immunization of BALB/c mice and mapping of B cell epitope. METHODS: The target epitope pp65(422-439) reactivity and B cell epitope mapping was examined in serum from pp65(422-439)-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis. RESULTS: Anti-pp65(422-439) antibody in serum either from patients with SLE or from pp65(422-439)-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65(422-439)-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65(422-439)-derived decapeptides, one dominant epitope, pp65(428-437), was identified in serum from pp65(422-439)-immunized mice and patients with SLE with anti-pp65(422-439) antibody. Epitope spreading from pp65(428-437) to pp65(430-439) was found in pp65(422-439)-immunized mice in which we generated monoclonal antibodies to pp65(425-434) and pp65(430-439). However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65(430-439)-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65(428-437.) CONCLUSIONS: Our data suggest that pp65(428-437) may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-017-1268-2) contains supplementary material, which is available to authorized users.