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

Ao HoHsieh; Chin Man Wang; Yeong Jian Jan Wu; Albert Chen; Ming I. Chang; Ji Yih Chen

doi:10.1186/s13075-017-1268-2

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

Ao HoHsieh, Chin Man Wang, Yeong Jian Jan Wu, Albert Chen, Ming I. Chang, Ji Yih Chen^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

18 Scopus citations

Abstract

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.

Original language	English
Article number	65
Journal	Arthritis Research and Therapy
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s13075-017-1268-2
State	Published - 21 03 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s).

Keywords

Anti-dsDNA antibody
Glomerulonephritis
Human cytomegalovirus phosphoprotein 65
Systemic lupus erythematosus

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10.1186/s13075-017-1268-2

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@article{b6cf96e2c6ff4eb990f1a0afdf00790c,

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

abstract = "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 pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope. Methods: The target epitope pp65422-439 reactivity 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. Results: Anti-pp65422-439 antibody 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-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and 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 pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.",

keywords = "Anti-dsDNA antibody, Glomerulonephritis, Human cytomegalovirus phosphoprotein 65, Systemic lupus erythematosus",

author = "Ao HoHsieh and Wang, {Chin Man} and Wu, {Yeong Jian Jan} and Albert Chen and Chang, {Ming I.} and Chen, {Ji Yih}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = mar,

day = "21",

doi = "10.1186/s13075-017-1268-2",

language = "英语",

volume = "19",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

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T1 - B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice

AU - HoHsieh, Ao

AU - Wang, Chin Man

AU - Wu, Yeong Jian Jan

AU - Chen, Albert

AU - Chang, Ming I.

AU - Chen, Ji Yih

PY - 2017/3/21

Y1 - 2017/3/21

N2 - 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 pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope. Methods: The target epitope pp65422-439 reactivity 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. Results: Anti-pp65422-439 antibody 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-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and 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 pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.

AB - 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 pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope. Methods: The target epitope pp65422-439 reactivity 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. Results: Anti-pp65422-439 antibody 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-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and 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 pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.

KW - Anti-dsDNA antibody

KW - Glomerulonephritis

KW - Human cytomegalovirus phosphoprotein 65

KW - Systemic lupus erythematosus

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U2 - 10.1186/s13075-017-1268-2

DO - 10.1186/s13075-017-1268-2

M3 - 文章

C2 - 28320458

AN - SCOPUS:85015735205

SN - 1478-6354

VL - 19

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 1

M1 - 65

ER -

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

Abstract

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