The role of VL gene structural determinants in the fine specificity of anti-DNA antibodies

Ajay K. Singh, Rosaria M R Gangemi

Research output: Contribution to journalArticle

Abstract

To investigate the structural contribution of the light chain of anti-DNA antibodies to fine specificity, the VKappa genes of two monoclonal anti-DNA antibodies, termed H241 and HI 02, were cloned and sequenced. HI02 and H241 are independently derived from MRL-lpr/lpr mice and differ in their line specificity: H241 binds dsDNA and normal glomeruli in vitro and deposits in the kidney in vivo whereas HI02 binds only ssDNA and does not deposit in the kidney. Both are encoded by nearly identical VH genes but different N and D regions. Our previous results have demonstrated that the VH gene for HI02 and H241 encodes eight other anti-DNA antibodies that also differed in fine specificity. This suggested that the gene product encoded by the VH 102/241 gene, may have intrinsic affinity for DNA, but is unlikely to determine fine specificity or nephritogenicity. In the present study we examined whether the VKappa gene might account for the difference in nephritogenicity. The complete nucleotide and deduced amino acid sequence of VK 102 and VK241 revealed that they are very dissimilar to each other (<60% homology). VK 241 defined a new member of the VKappa gene family and was moderately homologous to two other VK genes encoding anti-DNA antibodies and to one VK gene encoding an anti-histone antibody all from lupus strains of mice. In addition, sequence diversity in the VK CDR1 region and position 96 of the CDR3 region was observed that may be of signficance in determining fine specificity. VK 102 was highly homologous to two other VKappa genes, VKsl7.2 and VK C8.5, both encoding anti-DNA antibodies and members of the VK20gene family. It was striking that all three members of the VK 20 gene family code for DNA reactivity. This suggests that certain VKappa genes may also be used to repeatedly code for anti-DNA reactivity.

Original languageEnglish
Pages (from-to)65-75
Number of pages11
JournalAutoimmunity
Volume18
Issue number1
DOIs
Publication statusPublished - 1994

Fingerprint

Antinuclear Antibodies
Genes
DNA
Kidney
Histones
Anti-Idiotypic Antibodies
Amino Acid Sequence
Nucleotides
Monoclonal Antibodies

Keywords

  • Anti-DNA antibodies
  • Nephritogenicity
  • SLE
  • VL genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The role of VL gene structural determinants in the fine specificity of anti-DNA antibodies. / Singh, Ajay K.; Gangemi, Rosaria M R.

In: Autoimmunity, Vol. 18, No. 1, 1994, p. 65-75.

Research output: Contribution to journalArticle

@article{7dd53154ebb14ff59d3c676db6100fd8,
title = "The role of VL gene structural determinants in the fine specificity of anti-DNA antibodies",
abstract = "To investigate the structural contribution of the light chain of anti-DNA antibodies to fine specificity, the VKappa genes of two monoclonal anti-DNA antibodies, termed H241 and HI 02, were cloned and sequenced. HI02 and H241 are independently derived from MRL-lpr/lpr mice and differ in their line specificity: H241 binds dsDNA and normal glomeruli in vitro and deposits in the kidney in vivo whereas HI02 binds only ssDNA and does not deposit in the kidney. Both are encoded by nearly identical VH genes but different N and D regions. Our previous results have demonstrated that the VH gene for HI02 and H241 encodes eight other anti-DNA antibodies that also differed in fine specificity. This suggested that the gene product encoded by the VH 102/241 gene, may have intrinsic affinity for DNA, but is unlikely to determine fine specificity or nephritogenicity. In the present study we examined whether the VKappa gene might account for the difference in nephritogenicity. The complete nucleotide and deduced amino acid sequence of VK 102 and VK241 revealed that they are very dissimilar to each other (<60{\%} homology). VK 241 defined a new member of the VKappa gene family and was moderately homologous to two other VK genes encoding anti-DNA antibodies and to one VK gene encoding an anti-histone antibody all from lupus strains of mice. In addition, sequence diversity in the VK CDR1 region and position 96 of the CDR3 region was observed that may be of signficance in determining fine specificity. VK 102 was highly homologous to two other VKappa genes, VKsl7.2 and VK C8.5, both encoding anti-DNA antibodies and members of the VK20gene family. It was striking that all three members of the VK 20 gene family code for DNA reactivity. This suggests that certain VKappa genes may also be used to repeatedly code for anti-DNA reactivity.",
keywords = "Anti-DNA antibodies, Nephritogenicity, SLE, VL genes",
author = "Singh, {Ajay K.} and Gangemi, {Rosaria M R}",
year = "1994",
doi = "10.3109/08916939409014681",
language = "English",
volume = "18",
pages = "65--75",
journal = "Autoimmunity",
issn = "0891-6934",
publisher = "Informa Healthcare",
number = "1",

}

TY - JOUR

T1 - The role of VL gene structural determinants in the fine specificity of anti-DNA antibodies

AU - Singh, Ajay K.

AU - Gangemi, Rosaria M R

PY - 1994

Y1 - 1994

N2 - To investigate the structural contribution of the light chain of anti-DNA antibodies to fine specificity, the VKappa genes of two monoclonal anti-DNA antibodies, termed H241 and HI 02, were cloned and sequenced. HI02 and H241 are independently derived from MRL-lpr/lpr mice and differ in their line specificity: H241 binds dsDNA and normal glomeruli in vitro and deposits in the kidney in vivo whereas HI02 binds only ssDNA and does not deposit in the kidney. Both are encoded by nearly identical VH genes but different N and D regions. Our previous results have demonstrated that the VH gene for HI02 and H241 encodes eight other anti-DNA antibodies that also differed in fine specificity. This suggested that the gene product encoded by the VH 102/241 gene, may have intrinsic affinity for DNA, but is unlikely to determine fine specificity or nephritogenicity. In the present study we examined whether the VKappa gene might account for the difference in nephritogenicity. The complete nucleotide and deduced amino acid sequence of VK 102 and VK241 revealed that they are very dissimilar to each other (<60% homology). VK 241 defined a new member of the VKappa gene family and was moderately homologous to two other VK genes encoding anti-DNA antibodies and to one VK gene encoding an anti-histone antibody all from lupus strains of mice. In addition, sequence diversity in the VK CDR1 region and position 96 of the CDR3 region was observed that may be of signficance in determining fine specificity. VK 102 was highly homologous to two other VKappa genes, VKsl7.2 and VK C8.5, both encoding anti-DNA antibodies and members of the VK20gene family. It was striking that all three members of the VK 20 gene family code for DNA reactivity. This suggests that certain VKappa genes may also be used to repeatedly code for anti-DNA reactivity.

AB - To investigate the structural contribution of the light chain of anti-DNA antibodies to fine specificity, the VKappa genes of two monoclonal anti-DNA antibodies, termed H241 and HI 02, were cloned and sequenced. HI02 and H241 are independently derived from MRL-lpr/lpr mice and differ in their line specificity: H241 binds dsDNA and normal glomeruli in vitro and deposits in the kidney in vivo whereas HI02 binds only ssDNA and does not deposit in the kidney. Both are encoded by nearly identical VH genes but different N and D regions. Our previous results have demonstrated that the VH gene for HI02 and H241 encodes eight other anti-DNA antibodies that also differed in fine specificity. This suggested that the gene product encoded by the VH 102/241 gene, may have intrinsic affinity for DNA, but is unlikely to determine fine specificity or nephritogenicity. In the present study we examined whether the VKappa gene might account for the difference in nephritogenicity. The complete nucleotide and deduced amino acid sequence of VK 102 and VK241 revealed that they are very dissimilar to each other (<60% homology). VK 241 defined a new member of the VKappa gene family and was moderately homologous to two other VK genes encoding anti-DNA antibodies and to one VK gene encoding an anti-histone antibody all from lupus strains of mice. In addition, sequence diversity in the VK CDR1 region and position 96 of the CDR3 region was observed that may be of signficance in determining fine specificity. VK 102 was highly homologous to two other VKappa genes, VKsl7.2 and VK C8.5, both encoding anti-DNA antibodies and members of the VK20gene family. It was striking that all three members of the VK 20 gene family code for DNA reactivity. This suggests that certain VKappa genes may also be used to repeatedly code for anti-DNA reactivity.

KW - Anti-DNA antibodies

KW - Nephritogenicity

KW - SLE

KW - VL genes

UR - http://www.scopus.com/inward/record.url?scp=0027956387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027956387&partnerID=8YFLogxK

U2 - 10.3109/08916939409014681

DO - 10.3109/08916939409014681

M3 - Article

C2 - 7999957

AN - SCOPUS:0027956387

VL - 18

SP - 65

EP - 75

JO - Autoimmunity

JF - Autoimmunity

SN - 0891-6934

IS - 1

ER -