Abstract
Synthetic peptides corresponding to eight individual heavy chain complementarity-determining regions (CDR) of three human monoclonal IgM anti-IgG (rheumatoid factor [RF]) paraproteins elicited rabbit antibodies with markedly different properties. All antisera recognized the immunizing peptide, and several reacted with the isolated IgM heavy chain on immunoblots. However, only the antisera against peptides representing the third CDR bound consistently and specifically to the intact IgM-RF molecule. These data indicate that the third CDR of human mu chains comprises an immunodominant idiotype, and suggest that the D gene segment may be especially important in creating idiotypic diversity. Synthetic peptides corresponding to the third heavy chain CDR of human paraproteins may be clinically useful for the specific induction of antiidiotypic antibodies.
Full Text
The Full Text of this article is available as a PDF (399.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andrews D. W., Capra J. D. 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 idiotype. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3799–3803. doi: 10.1073/pnas.78.6.3799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berek C. The D segment defines the T15 idiotype: the immunoresponse of A/J mice to Pneumococcus pneumoniae. Eur J Immunol. 1984 Nov;14(11):1043–1048. doi: 10.1002/eji.1830141115. [DOI] [PubMed] [Google Scholar]
- Capra J. D., Kehoe J. M. Structure of antibodies with shared idiotypy: the complete sequence of the heavy chain variable regions of two immunoglobulin M anti-gamma globulins. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4032–4036. doi: 10.1073/pnas.71.10.4032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen P. P., Fong S., Normansell D., Houghten R. A., Karras J. G., Vaughan J. H., Carson D. A. Delineation of a cross-reactive idiotype on human autoantibodies with antibody against a synthetic peptide. J Exp Med. 1984 May 1;159(5):1502–1511. doi: 10.1084/jem.159.5.1502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen P. P., Houghten R. A., Fong S., Rhodes G. H., Gilbertson T. A., Vaughan J. H., Lerner R. A., Carson D. A. Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1784–1788. doi: 10.1073/pnas.81.6.1784. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clevinger B., Schilling J., Hood L., Davie J. M. Structural correlates of cross-reactive and individual idiotypic determinants on murine antibodies to alpha-(1 leads to 3) dextran. J Exp Med. 1980 May 1;151(5):1059–1070. doi: 10.1084/jem.151.5.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gridley T., Margolies M. N., Gefter M. L. The association of various D elements with a single-immunoglobulin VH gene segment: influence on the expression of a major cross-reactive idiotype. J Immunol. 1985 Feb;134(2):1236–1244. [PubMed] [Google Scholar]
- Kunkel H. G., Winchester R. J., Joslin F. G., Capra J. D. Similarities in the light chains of anti-gamma-globulins showing cross-idiotypic specificities. J Exp Med. 1974 Jan 1;139(1):128–136. doi: 10.1084/jem.139.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ledford D. K., Goñi F., Pizzolato M., Franklin E. C., Solomon A., Frangione B. Preferential association of kappa IIIb light chains with monoclonal human IgM kappa autoantibodies. J Immunol. 1983 Sep;131(3):1322–1325. [PubMed] [Google Scholar]
- Powell R., Agnello V. Characterization of complement-fixing activity and cross-idiotypes of rheumatoid factors in idiopathic mixed cryoglobulinemia. Clin Immunol Immunopathol. 1983 Oct;29(1):146–151. doi: 10.1016/0090-1229(83)90016-8. [DOI] [PubMed] [Google Scholar]
- Rudikoff S. Immunoglobulin structure--function correlates: antigen binding and idiotypes. Contemp Top Mol Immunol. 1983;9:169–209. doi: 10.1007/978-1-4684-4517-6_6. [DOI] [PubMed] [Google Scholar]
- Rudikoff S., Pawlita M., Pumphrey J., Mushinski E., Potter M. Galactan-binding antibodies. Diversity and structure of idiotypes. J Exp Med. 1983 Nov 1;158(5):1385–1400. doi: 10.1084/jem.158.5.1385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siebenlist U., Ravetch J. V., Korsmeyer S., Waldmann T., Leder P. Human immunoglobulin D segments encoded in tandem multigenic families. Nature. 1981 Dec 17;294(5842):631–635. doi: 10.1038/294631a0. [DOI] [PubMed] [Google Scholar]