Structural features of nephritogenic lupus autoantibodies

Myra T. Vargas, Kelvin Gustilo, Denise M. D'Andrea, Raghuram Kalluri, Mary H. Foster, Michael P. Madaio

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We have identified monoclonal antibodies derived from MRL-Ipr/Ipr lupus-prone mice that produced nephritis after passive transfer to normal mice. Our present goal was to elucidate the structural and immunochemical features of nephritogenic Ig that facilitate immune deposition. For this purpose the antigen binding properties, capacity to form immune deposits, and nucleotide sequence of a genetically related autoantibody subgroup were compared. The prototype, H147 (an IgG encoded by 7183/81X VH gene), produced glomerular and tubular basement membrane, mesangial immune deposits, and proliferative glomerulonephritis after passive transfer to normal mice. For comparison three other 7183/81X encoded anti-DNA IgG (H257, H171, and H8a) were evaluated (predicted heavy chain aa homology > 75%). H257 produced similar types of immune deposits as H147, and this was associated with nephritis; H8a produced predominantly mesangial deposits, whereas H171 did not produce significant deposits. Although their antigen binding profile to a panel of soluble autoantigens was variable, only H147 and H257 bound to both mesangial and aortic endothelial cell surfaces. V gene sequence analysis of the IgG suggests that individual residues, motifs, and conformations influence the autoantigen binding specificities that contributed to the observed differences in immune deposit formation.

Original languageEnglish (US)
Pages (from-to)62-69
Number of pages8
JournalMethods: A Companion to Methods in Enzymology
Volume11
Issue number1
DOIs
StatePublished - Jan 1 1997

Fingerprint

Autoantibodies
Deposits
Nephritis
Autoantigens
Immunoglobulin G
Antigens
Glomerular Basement Membrane
Glomerulonephritis
Genes
Sequence Analysis
Endothelial Cells
Monoclonal Antibodies
DNA
Endothelial cells
Conformations
Nucleotides
anti-IgG

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Vargas, M. T., Gustilo, K., D'Andrea, D. M., Kalluri, R., Foster, M. H., & Madaio, M. P. (1997). Structural features of nephritogenic lupus autoantibodies. Methods: A Companion to Methods in Enzymology, 11(1), 62-69. https://doi.org/10.1006/meth.1996.0388

Structural features of nephritogenic lupus autoantibodies. / Vargas, Myra T.; Gustilo, Kelvin; D'Andrea, Denise M.; Kalluri, Raghuram; Foster, Mary H.; Madaio, Michael P.

In: Methods: A Companion to Methods in Enzymology, Vol. 11, No. 1, 01.01.1997, p. 62-69.

Research output: Contribution to journalArticle

Vargas, MT, Gustilo, K, D'Andrea, DM, Kalluri, R, Foster, MH & Madaio, MP 1997, 'Structural features of nephritogenic lupus autoantibodies', Methods: A Companion to Methods in Enzymology, vol. 11, no. 1, pp. 62-69. https://doi.org/10.1006/meth.1996.0388
Vargas MT, Gustilo K, D'Andrea DM, Kalluri R, Foster MH, Madaio MP. Structural features of nephritogenic lupus autoantibodies. Methods: A Companion to Methods in Enzymology. 1997 Jan 1;11(1):62-69. https://doi.org/10.1006/meth.1996.0388
Vargas, Myra T. ; Gustilo, Kelvin ; D'Andrea, Denise M. ; Kalluri, Raghuram ; Foster, Mary H. ; Madaio, Michael P. / Structural features of nephritogenic lupus autoantibodies. In: Methods: A Companion to Methods in Enzymology. 1997 ; Vol. 11, No. 1. pp. 62-69.
@article{058bedd459d6445cb65ac9fc88b0896f,
title = "Structural features of nephritogenic lupus autoantibodies",
abstract = "We have identified monoclonal antibodies derived from MRL-Ipr/Ipr lupus-prone mice that produced nephritis after passive transfer to normal mice. Our present goal was to elucidate the structural and immunochemical features of nephritogenic Ig that facilitate immune deposition. For this purpose the antigen binding properties, capacity to form immune deposits, and nucleotide sequence of a genetically related autoantibody subgroup were compared. The prototype, H147 (an IgG encoded by 7183/81X VH gene), produced glomerular and tubular basement membrane, mesangial immune deposits, and proliferative glomerulonephritis after passive transfer to normal mice. For comparison three other 7183/81X encoded anti-DNA IgG (H257, H171, and H8a) were evaluated (predicted heavy chain aa homology > 75{\%}). H257 produced similar types of immune deposits as H147, and this was associated with nephritis; H8a produced predominantly mesangial deposits, whereas H171 did not produce significant deposits. Although their antigen binding profile to a panel of soluble autoantigens was variable, only H147 and H257 bound to both mesangial and aortic endothelial cell surfaces. V gene sequence analysis of the IgG suggests that individual residues, motifs, and conformations influence the autoantigen binding specificities that contributed to the observed differences in immune deposit formation.",
author = "Vargas, {Myra T.} and Kelvin Gustilo and D'Andrea, {Denise M.} and Raghuram Kalluri and Foster, {Mary H.} and Madaio, {Michael P.}",
year = "1997",
month = "1",
day = "1",
doi = "10.1006/meth.1996.0388",
language = "English (US)",
volume = "11",
pages = "62--69",
journal = "Methods in Enzymology",
issn = "0076-6879",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Structural features of nephritogenic lupus autoantibodies

AU - Vargas, Myra T.

AU - Gustilo, Kelvin

AU - D'Andrea, Denise M.

AU - Kalluri, Raghuram

AU - Foster, Mary H.

AU - Madaio, Michael P.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - We have identified monoclonal antibodies derived from MRL-Ipr/Ipr lupus-prone mice that produced nephritis after passive transfer to normal mice. Our present goal was to elucidate the structural and immunochemical features of nephritogenic Ig that facilitate immune deposition. For this purpose the antigen binding properties, capacity to form immune deposits, and nucleotide sequence of a genetically related autoantibody subgroup were compared. The prototype, H147 (an IgG encoded by 7183/81X VH gene), produced glomerular and tubular basement membrane, mesangial immune deposits, and proliferative glomerulonephritis after passive transfer to normal mice. For comparison three other 7183/81X encoded anti-DNA IgG (H257, H171, and H8a) were evaluated (predicted heavy chain aa homology > 75%). H257 produced similar types of immune deposits as H147, and this was associated with nephritis; H8a produced predominantly mesangial deposits, whereas H171 did not produce significant deposits. Although their antigen binding profile to a panel of soluble autoantigens was variable, only H147 and H257 bound to both mesangial and aortic endothelial cell surfaces. V gene sequence analysis of the IgG suggests that individual residues, motifs, and conformations influence the autoantigen binding specificities that contributed to the observed differences in immune deposit formation.

AB - We have identified monoclonal antibodies derived from MRL-Ipr/Ipr lupus-prone mice that produced nephritis after passive transfer to normal mice. Our present goal was to elucidate the structural and immunochemical features of nephritogenic Ig that facilitate immune deposition. For this purpose the antigen binding properties, capacity to form immune deposits, and nucleotide sequence of a genetically related autoantibody subgroup were compared. The prototype, H147 (an IgG encoded by 7183/81X VH gene), produced glomerular and tubular basement membrane, mesangial immune deposits, and proliferative glomerulonephritis after passive transfer to normal mice. For comparison three other 7183/81X encoded anti-DNA IgG (H257, H171, and H8a) were evaluated (predicted heavy chain aa homology > 75%). H257 produced similar types of immune deposits as H147, and this was associated with nephritis; H8a produced predominantly mesangial deposits, whereas H171 did not produce significant deposits. Although their antigen binding profile to a panel of soluble autoantigens was variable, only H147 and H257 bound to both mesangial and aortic endothelial cell surfaces. V gene sequence analysis of the IgG suggests that individual residues, motifs, and conformations influence the autoantigen binding specificities that contributed to the observed differences in immune deposit formation.

UR - http://www.scopus.com/inward/record.url?scp=0030916555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030916555&partnerID=8YFLogxK

U2 - 10.1006/meth.1996.0388

DO - 10.1006/meth.1996.0388

M3 - Article

VL - 11

SP - 62

EP - 69

JO - Methods in Enzymology

JF - Methods in Enzymology

SN - 0076-6879

IS - 1

ER -