B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice.
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 pp65336-439instigates autoimmunity, suggesting that pp65336-439contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439for immunization of BALB/c mice and mapping of B cell epitope.



The target epitope pp65422-439reactivity and B cell epitope mapping was examined in serum from pp65422-439-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis.



Anti-pp65422-439antibody in serum either from patients with SLE or from pp65422-439-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65422-439-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 pp65422-439-derived decapeptides, one dominant epitope, pp65428-437, was identified in serum from pp65422-439-immunized mice and patients with SLE with anti-pp65422-439antibody. Epitope spreading from pp65428-437to pp65430-439was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434and pp65430-439. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65430-439-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65428-437.CONCLUSIONS: Our data suggest that pp65428-437may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.
Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
Ao
A
HoHsieh
Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan, Republic of China.
Chin Man
CM
Wang
Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Taoyuan, 33375, Taiwan, Republic of China.
Yeong-Jian Jan
YJ
Wu
Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA.
Albert
A
Chen
Biologics, Ruen Huei Biopharmaceuticals, 1F, No.16-1, Ln. 119, Sec. 1, Roosevelt Rd., Jhongjheng Dist., Taipei, Taiwan, Republic of China.
Ming-I
MI
Chang
Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Taoyuan, 33375, Taiwan, Republic of China. jychen31@adm.cgmh.org.tw.
Ji-Yih
JY
Chen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D015153:Blotting, Western; D003429:Cross Reactions; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000821:virology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D055815:Young Adult
D000914:Antibodies, Viral; D001323:Autoantibodies; D018985:Epitopes, B-Lymphocyte; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa
Anti-dsDNA antibody; Glomerulonephritis; Human cytomegalovirus phosphoprotein 65; Systemic lupus erythematosus