Skip to main content
SpringerLink
Log in

Molecular localization of human IgG anti-F(ab′)2 reactivity with variable- and constant-region λ light-chain epitopes

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Human IgG antibodies reacting with antigenic determinants on F(ab′)2 fragments represent generic antiidiotypic antibodies present in the serum of normal individuals. Additionally, the titers of these antibodies in the sera of patients with systemic lupus erythematosus (SLE) are inversely related to disease activity. Because these autoantibodies recognize predominantly light chain-related epitopes, especially λ type, we synthesized constant (C)λ- and variable (V)λ-related overlapping 7-mer peptides on polypropylene pins to determine anti-F(ab′)2-reactive epitopes on humanλ light chains. ELISA reactivity of affinity-purified anti-F(ab′)2 antibodies obtained from normal individuals and from patients with SLE, as well as murine anti-human light-chain monoclonal antibodies specific for Cλ and Vλ subgroup-related determinants, was tested using the overlapping 7-mers of humanλ light-chain sequence. The patterns of reactivity against Cλ-related peptides were similar in both normal and SLE-derived anti-F(ab′)2 antibodies. However, reactivity profiles against Vλ-related peptides were distinctively different between the normal and the SLE-associated anti-F(ab′)2 autoantibodies. A decrease in reactivity among the SLE IgG anti-F(ab′)2 antibodies was noted for particular amino acid Vλ complementarity-determining region (CDR) residues, including glycine at positions 27 and 54, alanine at 16 and 37, and tyrosine at 28 and 91. This different pattern of reactivity from normal may indicate that in SLE there is a failure of antiidiotypic control mechanisms, as reflected by a defect in production of antibody to immunodominant Vλ CDR residues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Nasu H, Chia DS, Taniguchi O, Barnett EV: Characterization of anti-F(ab′)2 antibodies in SLE patients: Evidence for crossreacting auto-antiidiotypic antibodies. Clin Immunol Immunopathol 25:80–90, 1992

    Google Scholar 

  2. Silvestris F, Bankhurst AD, Searles RP, Williams RC Jr: Studies of anti-F(ab′)2 antibodies and possible immunologic control mechanisms in systemic lupus erythematosus. Arth Rheum 27:1387–1396, 1984

    Google Scholar 

  3. Silvestris F, Searles RP, Bankhurst AD, Williams RC Jr: Family distribution of anti-F(ab′)2 antibodies in relatives of patients with systemic lupus erythematosus. Clin Exp Immunol 60:329–338, 1985

    PubMed  Google Scholar 

  4. Silvestris F, Williams RC Jr, Searles RP: Human anti-F(ab′)2 antibodies and pepsin agglutinators react with Fv determinants. Scand J Immunol 23:499–508, 1986

    PubMed  Google Scholar 

  5. Silvestris F, Rots N, Yancey WB, Malone C, Searles R, Solomon A, Dammacco F, Williams RC Jr: Monoclonal antibodies against human anti-F(ab′)2 antibodies react with light chain epitopes. Clin Immunol Immunopathol 59:139–155, 1991

    PubMed  Google Scholar 

  6. Yancey WB, Silvestris F, Conlon M, Rodriguez M, Malone CC, Williams RC Jr: Human anti-F(ab′)2 antibodies show preferential reactivity for F(ab′)2 molecules bearingα light chains. Clin Immunol Immunopathol 65:176–182, 1992

    PubMed  Google Scholar 

  7. Geysen HM, Rodda SJ, Mason TJ, Tribbick G, Schoofs PG: Strategies for epitope analysis using peptide synthesis. J Immunol Methods 102:259–274, 1987

    PubMed  Google Scholar 

  8. Getzoff ED, Geysen HM, Rodda SJ, Alexander H, Tainer JA, Lerner RA: Mechanisms of antibody binding to a protein. Science 235:1191–1196, 1987

    PubMed  Google Scholar 

  9. Williams RC Jr, Kievit E, Tsuchiya N, Malone CC, Hutt-Fletcher L: Differential mapping of Fcγ-binding and monoclonal-antibody-reactive epitopes on gE, the Fcγ-binding glycoprotein of herpes simplex virus type 1. J Immunol 149:2415–2427, 1992

    PubMed  Google Scholar 

  10. Williams RC Jr, Malone CC, Tsuchiya N: Rheumatoid factors from patients with RA react with humanβ2-microglobulin. J Immunol 149:1104–1113, 1992

    PubMed  Google Scholar 

  11. Williams RC Jr, Malone CC: Antigenic epitopes on humanβ 2m reacting with monoclonal antibodies. J Lab Clin Med 121:805–820, 1993

    PubMed  Google Scholar 

  12. Williams RC Jr, Malone CC, Harley JB: Rheumatoid factors from patients with rheumatoid arthritis react with tryptophane 60 and 95, lysine 58 and arginine 97 on humanβ 2-microglobulin. Arth Rheum 36:916–926, 1993

    Google Scholar 

  13. Williams RC Jr, Staud R, Malone CC, Payabyab J, Byres L, Underwood D: Epitopes on proteinase-3 recognized by antibodies from patients with Wegener's granulomatosis. J Immunol 152: 4722–4737, 1994

    PubMed  Google Scholar 

  14. Solomon A, Weiss DT, Murphy C, Fu SM, Robbins DL: Chemical and serological characterization of humanλ VIII light chains. J Immunol 153:1658–1664, 1994

    PubMed  Google Scholar 

  15. Novotny J, Handschumacher M, Haber E: Location of antigenic epitopes on antibody molecules. J Mol Biol 189:715–721, 1986

    PubMed  Google Scholar 

  16. Kabat EA, Wu TT, Reid-Miller M, Perry HM, Gottesman KS: Sequences of Proteins of Immunological Interest, 4th ed. Washington, DC, US Department of Health and Human Services, 1987, p 287

    Google Scholar 

  17. Marchalonis JJ, Dedeoglu F, Kaymaz H, Schluter SF, Edmundson AB: Antigenic mapping of a human A light chain: Correlation with three dimensional structure. J Protein Chem 11:129–137, 1992

    PubMed  Google Scholar 

  18. Peterson C, Malone CC, Williams RC Jr: Rheumatoid-factor-reactive sites on CH3 established by overlapping 7-mer peptide epitope analysis. Mol Immunol 32:57–75, 1995

    PubMed  Google Scholar 

  19. Rath S, Stanley CM, Steward MW: An inhibition enzyme immunoassay for estimating relative antibody affinity and affinity heterogeneity. J Immunol Methods 106:245, 1988

    PubMed  Google Scholar 

  20. Abe M, Goto T, Kennel SJ, Wolfenbarger D, Macy SD, Weiss DT, Solomon A: Production and immunodiagnostic applications of anti-human light chain monoclonal antibodies. Am J Clin Pathol 100:67–74, 1993

    PubMed  Google Scholar 

  21. Williams RC Jr, Silvestris F, Malone CC: Normal human sera contain IgG anti-idiotypic antibody to CDR regions of two different monoclonal anti-DNA antibodies bearing either the 16/6 or the 3I, F4 Id markers. Arth Rheum 37:S 316, 930, 1994

    Google Scholar 

  22. Williams RC Jr, Malone CC, Silvestris F: CDR molecular localization of possible anti-idiotypic anti-DNA antibodies in normal subjects, SLE patients and SLE first-degree relatives. J Lab Clin Med 126:44–56, 1995

    PubMed  Google Scholar 

  23. Williams RC Jr, Malone CC: Rheumatoid-factor-reactive sites on CH2 established by analysis of overlapping peptides of primary sequence. Scand J Immunol 40:443–456, 1994

    PubMed  Google Scholar 

  24. Johansson PJH, Malone C, Swietnicki W, Dunn BM, Williams RC Jr: Fv structure of monoclonal antibody II-481 against herpes simplex virus Fcγ-binding glycoprotein gE contains immunodom- inant CDR epitopes which react with human IgM rheumatoid factors. J Exp Med 180:1873–1888, 1994

    PubMed  Google Scholar 

  25. Kolaskar AS, Kulkarni-Kale U: Sequence alignment approach to pick up conformationally similar protein fragments. J Mol Biol 223:1053–1061, 1992

    PubMed  Google Scholar 

  26. Terness P, Kohl I, Hubener G, Battistutta R, Moroder L, Welschof M, Duffler C, Finger M, Hain C, Jung M, Opelz G: The natural human IgG anti-F(ab′)2 antibody recognizes a conformational IgG1 hinge epitope. J Immunol 154:6446–6452, 1995

    PubMed  Google Scholar 

  27. Williams RC Jr, Malone CC, Silvestris F: Anti-F(ab′)2 antibody is linked through idiotypic networks to production of anti-DNA and other autoantibodies with anti-nuclear specificity (submitted for publication)

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, Florida

    Ralph C. Williams Jr., Christine C. Malone & Franco Silvestris

  2. Human Immunology and Cancer Program, Department of Medicine, University of Tennessee, Knoxville, Tennessee

    Alan Solomon

Authors
  1. Ralph C. Williams Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christine C. Malone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Franco Silvestris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alan Solomon
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Williams, R.C., Malone, C.C., Silvestris, F. et al. Molecular localization of human IgG anti-F(ab′)2 reactivity with variable- and constant-region λ light-chain epitopes. J Clin Immunol 15, 349–362 (1995). https://doi.org/10.1007/BF01541325

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01541325

Key words

Search

Navigation