Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Nov 1;154(5):1525–1538. doi: 10.1084/jem.154.5.1525

Idiotypy of clonal responses to influenza virus hemagglutinin

PMCID: PMC2186501  PMID: 7299346

Abstract

Anti-idiotype antisera were raised in syngeneic (BALB/c mice) and homologous (A/J mice) systems to study the cross-reactive idiotypes among monoclonal antibodies to PR8 and B/Lee virus HA and the expression of these idiotypes during primary and secondary antiviral responses of BALB/c mice. Extensive idiotypic cross-reactivity was demonstrated among monoclonal antibodies specific for distinct antigenic determinants on PR8 hemagglutinin (HA). The study of idiotypy of monoclonal antibodies against the same or overlapping antigenic determinants on B/Lee HA showed that these monoclonal antibodies may bear (a) a true individual idiotype not shared by other monoclonal antibodies, (b) idiotypes shared by few monoclonal antibodies, and (c) true cross-reactive idiotypes shared by all of these monoclonal antibodies. In contrast, no cross-reactive idiotypes were detectable among monoclonal antibodies to B/Lee HA and monoclonal antibodies to PR8 HA. Furthermore, we have shown that the anti-idiotype antibodies we used recognize determinants on monoclonal antibodies closely associated with antigenic binding sites. Finally, studies of the idiotypes expressed during primary and secondary antiviral HA responses of mice immunized with B/Lee virus revealed persistence of some idiotypes during both primary and secondary responses, whereas others were only expressed in the primary or secondary response.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bona C. A., Heber-Katz E., Paul W. E. Idiotype-anti-idiotype regulation. I. Immunization with a levan-binding myeloma protein leads to the appearance of auto-anti-(anti-idiotype) antibodies and to the activation of silent clones. J Exp Med. 1981 Apr 1;153(4):951–967. doi: 10.1084/jem.153.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bona C., Lieberman R., Chien C. C., Mond J., House S., Green I., Paul W. E. Immune response to levan. I. Kinetics and ontogeny of anti-levan and anti-inulin antibody response and of expression of cross-reactive idiotype. J Immunol. 1978 Apr;120(4):1436–1442. [PubMed] [Google Scholar]
  3. Bona C., Mond J. J., Stein K. E., House S., Lieberman R., Paul W. E. Immune response to levan. III. The capacity to produce anti-inulin antibodies and cross-reactive idiotypes appears late in ontogeny. J Immunol. 1979 Oct;123(4):1484–1490. [PubMed] [Google Scholar]
  4. Bona C., Mongini P. K., Stein K. E., Paul W. E. Anti-immunoglobulin antibodies. I. Expression of cross-reactive idiotypes and Ir gene control of the response to IgG2a of the b allotype. J Exp Med. 1980 Jun 1;151(6):1334–1348. doi: 10.1084/jem.151.6.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown J. C., Rodkey L. S. Autoregulation of an antibody response via network-induced auto-anti-idiotype. J Exp Med. 1979 Jul 1;150(1):67–85. doi: 10.1084/jem.150.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cancro M. P., Wylie D. E., Gerhard W., Klinman N. R. Patterned acquisition of the antibody repertoire: diversity of the hemagglutinin-specific B-cell repertoire in neonatal BALB/c mice. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6577–6581. doi: 10.1073/pnas.76.12.6577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hierholzer J. C., Suggs M. T. Standardized viral hemagglutination and hemagglutination-inhibition tests. I. Standardization of erythrocyte suspensions. Appl Microbiol. 1969 Nov;18(5):816–823. doi: 10.1128/am.18.5.816-823.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hiernaux J., Bona C., Baker P. J. Neonatal treatment with low doses of anti-idiotypic antibody leads to the expression of a silent clone. J Exp Med. 1981 Apr 1;153(4):1004–1008. doi: 10.1084/jem.153.4.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ju S. T., Benacerraf B., Dorf M. E. Genetic control of a shared idiotype among antibodies directed to distinct specificities. J Exp Med. 1980 Jul 1;152(1):170–182. doi: 10.1084/jem.152.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kabat E. A. Origins of antibody complementarity and specificity--hypervariable regions and minigene hypothesis. J Immunol. 1980 Sep;125(3):961–969. [PubMed] [Google Scholar]
  12. Karol R., Reichlin M., Noble R. W. Idiotypic cross-reactivity between antibodies of different specificities. J Exp Med. 1978 Dec 1;148(6):1488–1497. doi: 10.1084/jem.148.6.1488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kunkel H. G., Agnello V., Joslin F. G., Winchester R. J., Capra J. D. Cross-idiotypic specificity among monoclonal IgM proteins with anti- -globulin activity. J Exp Med. 1973 Feb 1;137(2):331–342. doi: 10.1084/jem.137.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kunkel H. G., Joslin F., Hurley J. Blocking of certain antigenic sites in the F(ab) region by combination of univalent fragments of Rh antibodies with red cell antigens. J Immunol. 1976 Jun;116(6):1532–1535. [PubMed] [Google Scholar]
  15. Kunkel H. G., Mannik M., Williams R. C. Individual Antigenic Specificity of Isolated Antibodies. Science. 1963 Jun 14;140(3572):1218–1219. doi: 10.1126/science.140.3572.1218. [DOI] [PubMed] [Google Scholar]
  16. Laver W. G., Air G. M., Webster R. G., Gerhard W., Ward C. W., Dopheide T. A. Antigenic drift in type A influenza virus: sequence differences in the hemagglutinin of Hong Kong (H3N2) variants selected with monoclonal hybridoma antibodies. Virology. 1979 Oct 15;98(1):226–237. doi: 10.1016/0042-6822(79)90540-3. [DOI] [PubMed] [Google Scholar]
  17. Lieberman R., Potter M., Humphrey W., Jr, Chien C. C. Idiotype of inulin-binding antibodies and myeloma proteins controlled by genes linked to the allotype locus of the mouse. J Immunol. 1976 Dec;117(6):2105–2111. [PubMed] [Google Scholar]
  18. Lieberman R., Potter M., Humphrey W., Jr, Mushinski E. B., Vrana M. Multiple individual and cross-specific indiotypes on 13 levan-binding myeloma proteins of BALB/c mice. J Exp Med. 1975 Jul 1;142(1):106–119. doi: 10.1084/jem.142.1.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lubeck M. D., Schulman J. L., Palese P. Antigenic variants of influenza viruses: marked differences in the frequencies of variants selected with different monoclonal antibodies. Virology. 1980 Apr 30;102(2):458–462. doi: 10.1016/0042-6822(80)90114-2. [DOI] [PubMed] [Google Scholar]
  20. MacDonald A. B., Nisonoff A. Quantitative investigations of idiotypic antibodies. 3. Persistence and variations of idiotypic specificities during the course of immunization. J Exp Med. 1970 Mar 1;131(3):583–601. doi: 10.1084/jem.131.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mongini P. K., Stein K. E., Paul W. E. T cell regulation of IgG subclass antibody production in response to T-independent antigens. J Exp Med. 1981 Jan 1;153(1):1–12. doi: 10.1084/jem.153.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nakajima K., Desselberger U., Palese P. Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature. 1978 Jul 27;274(5669):334–339. doi: 10.1038/274334a0. [DOI] [PubMed] [Google Scholar]
  23. Oudin J., Cazenave P. A. Similar idiotypic specificities in immunoglobulin fractions with different antibody functions or even without detectable antibody function. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2616–2620. doi: 10.1073/pnas.68.10.2616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oudin J., Michel M. Idiotypy of rabbit antibodies. II. Comparison of idiotypy of various kinds of antibodies formed in the same rabbits against Salmonella typhi. J Exp Med. 1969 Sep 1;130(3):619–642. doi: 10.1084/jem.130.3.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Palese P., Schulman J. Isolation and characterization of influenza virus recombinants with high and low neuraminidase activity. Use of 2-(3'-methoxyphenyl)-n-acetylneuraminic acid to identify cloned populations. Virology. 1974 Jan;57(1):227–237. doi: 10.1016/0042-6822(74)90123-8. [DOI] [PubMed] [Google Scholar]
  26. Porter A. G., Barber C., Carey N. H., Hallewell R. A., Threlfall G., Emtage J. S. Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA. Nature. 1979 Nov 29;282(5738):471–477. doi: 10.1038/282471a0. [DOI] [PubMed] [Google Scholar]
  27. Portner A., Webster R. G., Bean W. J. Similar frequencies of antigenic variants in Sendai, vesicular stomatitis, and influenza A viruses. Virology. 1980 Jul 15;104(1):235–238. doi: 10.1016/0042-6822(80)90382-7. [DOI] [PubMed] [Google Scholar]
  28. Reiss C. S., Schulman J. L. Cellular immune responses of mice to influenza virus infection. Cell Immunol. 1980 Dec;56(2):502–509. doi: 10.1016/0008-8749(80)90124-0. [DOI] [PubMed] [Google Scholar]
  29. Wells J. V., Fudenberg H. H., Givol D. Localization of idiotypic antigenic determinants in the Fv region of murine myeloma protein MOPC-315. Proc Natl Acad Sci U S A. 1973 May;70(5):1585–1587. doi: 10.1073/pnas.70.5.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wiley D. C., Wilson I. A., Skehel J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981 Jan 29;289(5796):373–378. doi: 10.1038/289373a0. [DOI] [PubMed] [Google Scholar]
  31. Yewdell J. W., Webster R. G., Gerhard W. U. Antigenic variation in three distinct determinants of an influenza type A haemagglutinin molecule. Nature. 1979 May 17;279(5710):246–248. doi: 10.1038/279246a0. [DOI] [PubMed] [Google Scholar]
  32. de Saint Martin J., Mukoyama H., Eyquem A. Evolution pendant 9 ans de l'idiotypie des anticorps anti-Rh chez un donneur de sang. C R Acad Sci Hebd Seances Acad Sci D. 1978 Apr 17;286(15):1183–1186. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES