Summary
Two mouse hybridoma antibodies, G6 and H1, with specificity for idiotypic determinants on the heavy chain of human IgM-RF have been produced. Idiotopes recognized by G6 and H1 were expressed on 5/12 and 2/12 RF paraproteins from the Wa idiotype group respectively, but not on paraproteins lacking rheumatoid factor (RF) activity. Inhibition experiments demonstrated that G6 and H1-specific epitopes were located on (or close to) the antibody binding site of RFs, and measurable on the heavy chain but not their light chains. However, it was concluded that the quaternary structure of the antibody-binding site was important for the optimal expression of both idiotopes. The idiotope recognized by G6 was also detected on polyclonal RFs in unfractionated sera from 8/14 patients with rheumatoid arthritis (RA). The results suggest that the G6 idiotope is a highly conserved determinant on the antibody-binding site of RF. These monoclonal antibodies will allow characterization of RF clonality in RA.
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Kunkel HG, Muller-Eberhard HJ, Fudenberg H, Tomasi TB (1961) Gamma globulin complexes in rheumatoid arthritis and certain other conditions. J Clin Invest 40:117–129
Zvaifler NJ (1973) The immunopathology of joint inflammation in rheumatoid arthritis. Adv Immunol 13:265–336
Carson DA, Pasquali J-L, Tsoukas CD, Fong S, Slovin SF, Lawrence S (1981) Physiology and pathology of rheumatoid factors. Springer Semin Immunopathol 4:161–179
Kunkel HG, Posnett DN, Pernis B (1983) Anti-immunoglobulins and their idiotypes: are they part of the immune network? Ann NY Acad Sci 418:324–329
Kunkel HG, Agnello V, Joslin FG, Winchester RJ, Capra JD (1973) Cross-idiotypic specificity among monoclonal IgM proteins with anti-gamma globulin activity. J Exp Med 137:331–342
Powell R, Agnello V (1983) Characterization of complement-fixing activity of rheumatoid factors in idiopathic mixed cryoglobulinemia. Clin Immunol Immunopathol 29:146–151
Capra JD, Kehoe JM (1974) Structure of antibodies with shared idiotypy: the complete sequence of the heavy chain variable region of two immunoglobulin M antigamma globulins. Proc Natl Acad Sci USA 71:4032–4036
Albutt EC, Hawker PC, Hine KR, Northan BE (1981) Diagnosis of gamma heavy chain disease. Ann Clin Biochem 18:207–210
Nik Jaafar MI, Lowe JA, Ling NR, Jefferis R (1983) Immunogenic and antigenic epitopes of immunoglobulins-V. Reactivity of a panel of monoclonal antibodies with sub-fragments of human Fc gamma and abnormal paraproteins having deletions. Mol Immunol 20:679–686
Plaut GA, Tomasi TB (1970) Immunoglobulin M: pentameric Fcu fragments released by trypsin at higher temperatures. Proc Natl Acad Sci USA 65:318–322
Walker M, Hardie D, Lowe J, Ling NR, De Lange G, Jefferis R (1985) Immunogenicity and antigenicity of immunoglobulins: XII-Intact light chain and heavy chain isotype-restricted VK-associated epitopes. Immunology 55:205–211
Kohler G, Milstein C (1975) Continuous culture of fused cells secreting antibody of a defined specificity. Nature 256:495–497
Lowe J, Hardie D, Jefferis R, Ling NR, Drysdale P, Richardson P, Raykindalia C, Catty D, Appleby P, Drew R, MacLennan ICM (1981) Properties of monoclonal antibodies to human immunoglobulin kappa and lambda chains. Immunology 42:649–659
Ling NR, Bishop S, Jefferis R (1977) Use of antibody coated red cells for the sensitive detection of antigen and in rosette tests for cells bearing surface immunoglobulins. J Immunol Methods 15:279–289
Carson DA, Fong S (1983) A common idiotope on human rheumatoid factors identified by a hybridoma antibody. Mol Immunol 20:1081–1087
Kunkel HG, Winchester RJ, Joslin FG, Capra JD (1974) Similarities in the light chains of anti-gamma globulins showing cross-idiotypic specificities. J Exp Med 139:128–136
Klapper DG, Capra JD (1976) The amino acid sequence of the variable regions of the light chains from two idiotypically cross-reactive IgM anti-gamma globulins. Ann Immunol (Paris) 127C:261–271
Andrews DW, Capra JD (1981) Complete amino acid sequence of variable domains from two monoclonal human anti-gamma globulins of the Wa cross-idiotypic group: suggestion that the J segments are involved in the structural correlate of the idiotope. Proc Natl Acad Sci USA 78:3799–3803
Chen PP, Goni F, Houghten RA, Fong S, Goldfien R, Vaughan JH, Frangione B, Carson DA (1985) Characterization of human rheumatoid factors with seven antiidiotypes induced by synthetic hypervariable region peptides. J Exp Med 162:487–500
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Mageed, R.A., Dearlove, M., Goodall, D.M. et al. Immunogenic and antigenic epitopes of immunoglobulins XVII-monoclonal antibodies reactive with common and restricted idiotopes to the heavy chain of human rheumatoid factors. Rheumatol Int 6, 179–183 (1986). https://doi.org/10.1007/BF00541285
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DOI: https://doi.org/10.1007/BF00541285