Immunoglobulin variable region sequences of humanmonoclonal anti-DNA, antibodies

Rahman, Anisur; Latchman, David S.; Isenberg, David

doi:10.1016/s0049-0172(98)80031-0

Cited by 29 publications

(27 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this distribution is similar to the normal repertoire, supporting the contention that the choice of V genes encoding autoantibodies follows patterns similar to those seen in normal subjects. Rahman and coworkers (84) have also compared the V gene usage of IgM and IgG human anti-DNA monoclonal antibodies and detected only moderate differences. The IgGbearing monoclonal antibodies frequently used the V gene 2a2 (5 of 6 IgG V employing monoclonal antibodies), whereas 2a2 was not used in the IgM antibodies.…”

Section: Selective Influences Shaping the Ig V Gene Repertoirementioning

confidence: 99%

Immunoglobulin variable-region gene usage in systemic autoimmune diseases

Dörner¹,

Lipsky²

2001

Arthritis & Rheumatism

View full text Add to dashboard Cite

Section: Selective Influences Shaping the Ig V Gene Repertoirementioning

confidence: 99%

Immunoglobulin variable-region gene usage in systemic autoimmune diseases

Dörner¹,

Lipsky²

2001

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…Similarly, Arg, Lys, and Asn residues occur commonly in the CDRs of human and murine Abs to dsDNA (20,21), frequently as a result of somatic mutation (22). The anti-dsDNA affinity of F(abЈ) 2 and Abs isolated from patients with lupus has been shown to correlate with the presence of Arg residues in CDRs of both H (23) and L chains (24).…”

mentioning

confidence: 99%

Arginine Residues Are Important in Determining the Binding of Human Monoclonal Antiphospholipid Antibodies to Clinically Relevant Antigens

Giles

Lambrianides

Pattni

et al. 2006

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

In the antiphospholipid syndrome (APS), antiphospholipid Abs (aPL) bind to anionic phospholipids (PL) and various associated proteins, especially β2-glycoprotein I (β2GPI) and prothrombin. In the present study, we show that altering specific Arg residues in the H chain of a human pathogenic β2GPI-dependent aPL, IS4, has major effects on its ability to bind these clinically important Ags. We expressed whole human IgG in vitro by stable transfection of Chinese hamster ovary cells with expression plasmids containing different VH and VL sequences. VH sequences were derived from IS4 by altering the number of Arg residues in CDR3. VL sequences were those of IS4, B3 (anti-nucleosome Ab), and UK4 (β2GPI-independent aPL). Binding of the expressed H/L chain combinations to a range of anionic, neutral, and zwitterionic PL, as well as prothrombin, β2GPI, dsDNA, and chicken OVA, was determined by ELISA. Of four Arg residues in IS4VH CDR3 substituted to Ser, two at positions 100 and 100g, reduced binding to all Ags, while two at positions 96 and 97 reduced binding to β2GPI but increased or decreased binding to different PL. Eleven of 14 H/L chain combinations displayed weak binding to OVA with Arg to Ser replacements of all four Arg residues enhancing binding to this Ag. Only one H/L chain combination bound neutral PL and none bound dsDNA; hence, these effects are particularly relevant to Ags important in antiphospholipid syndrome. We hypothesize that these four Arg residues have developed as a result of somatic mutations driven by an Ag containing both PL and β2GPI.

show abstract

“…In many but not all antidsDNA antibodies, the increased presence in the CDRs of basic amino acid residues which may potentially interact with DNA, such as arginine (R), lysine (L) and asparagine (N), has been observed, indicating that DNA is a stimulating antigen. These residues were shown to be encoded by somatic mutations and/or are germline introduced [1] and may dramatically increase the anti-dsDNA affinity [2].…”

Section: Objectivementioning

confidence: 99%

“…The antibody obviously bound to dsDNA already in germline configuration. Several other anti-dsDNA antibodies have been described whose dsDNA specificity was germline encoded or maintained following the reversion of their somatic mutations [1,2]. Other gene elements than CDR1 or CDR2 with their mutations may be responsible for dsDNA binding.…”

Section: Objectivementioning

confidence: 99%

“…Discussion: We discuss the approach to constructing scFv fragments as a tool to study autoantibody maturation. Copyright © 2001 S. Karger AG, Basel Analysis of the heavy-and light-chain genes of anti-double-stranded (ds) DNA antibodies from patients with systemic lupus erythematosus has revealed isotype switching, somatic mutations and, in many cases, clustering of replacement mutations in the complementary determining regions (CDRs) [1]. …”

mentioning

confidence: 99%

See 1 more Smart Citation

Development of Single-Chain Fv Fragments from a Human Anti-Double-Stranded DNA Antibody to Study the Influence of Somatic Mutations on Antigen Binding

Kersten

Niemann²,

Jahn³

2001

Exp Clin Immunogenet

View full text Add to dashboard Cite

Objective: The monoclonal IgG anti-double-stranded (ds) DNA antibody 32B9, obtained from a patient with systemic lupus erythematosus, was found to be encoded by somatically mutated immunoglobulin genes. We examined the input of several somatic mutations into antibody specificity and affinity. Methods: Five single-chain (sc) Fv fragments [variable domain of the heavy chain (V_H)-linker-variable domain of the light chain (V_L)] derived from 32B9 were constructed and expressed in Escherichia coli. These scFv fragments contained V_H or V_L fragments, differing in the somatic mutation pattern. The antigen binding features of the 32B9 IgG were compared with the corresponding scFv fragments, and the binding to DNA of all fragments was analyzed by ELISA. Binding constants to dsDNA were determined by surface plasmon resonance and ELISA. Results: The scFv 32B9 reflected the binding features of the 32B9 IgG. Independently of the somatic mutations, all scFv fragments bound to dsDNA in ELISA. The affinity data indicated that the mutations studied had only a marginal effect on affinity maturation of the 32B9. Discussion: We discuss the approach to constructing scFv fragments as a tool to study autoantibody maturation.

show abstract

Immunoglobulin variable region sequences of humanmonoclonal anti-DNA, antibodies

Cited by 29 publications

References 70 publications

Immunoglobulin variable-region gene usage in systemic autoimmune diseases

Immunoglobulin variable-region gene usage in systemic autoimmune diseases

Arginine Residues Are Important in Determining the Binding of Human Monoclonal Antiphospholipid Antibodies to Clinically Relevant Antigens

Development of Single-Chain Fv Fragments from a Human Anti-Double-Stranded DNA Antibody to Study the Influence of Somatic Mutations on Antigen Binding

Contact Info

Product

Resources

About