Abstract
A new cross-reactive idiotope family (CRIAD8) is described that contains subpopulations of antibodies binding to different epitopes. One subpopulation occurs naturally in normal sera from strain A mice, is found mainly on IgG2 and IgG3 subclasses, does not bind p- azobenzenearsonate (ABA)+, does not express CRI5Ci, and can be selectively stimulated by low doses of antiidiotype antibody (AD8). The second subpopulation is not found in normal serum, binds ABA, is found on all IgG subclasses, expresses CRI5Ci, and is selectively stimulated by ABA-conjugated proteins. Since CRIAD8 was found on both subpopulations of antibody, and since each subpopulation could be selectively expanded, it was possible to study the effect that expansion of the ABA- CRIAD8+ set had on subsequent responses elicited by ABA-keyhole limpet hemocyanin (KLH) in the ABA+ CRIAD8+ set. In these experiments, prior immunization with AD8 restricted the subsequent response of the ABA+ CRIAD8+ set to ABA-KLH. Furthermore, only those doses of AD8 that stimulated the ABA-CRIAD8+ set reduced the responsiveness of the ABA+ CRIAD8+ set to ABA-KLH, suggesting that the two phenomena are causally related. These findings argue that CRIAD8 correlates well with a regulatory idiotope and that immune responses by lymphocyte clones that have different antigen-binding specificities can affect one another as a result of their sharing such an idiotope. These results strongly favor a network organization of the immune system.
Full Text
The Full Text of this article is available as a PDF (1.7 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adorini L., Harvey M., Sercarz E. E. The fine specificity of regulatory T cells. IV. Idiotypic complementarity and antigen-bridging interactions in the anti-lysozyme response. Eur J Immunol. 1979 Nov;9(11):906–909. doi: 10.1002/eji.1830091113. [DOI] [PubMed] [Google Scholar]
- 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]
- Dzierzak E. A., Janeway C. A., Jr Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. III. Detection of Id-460 in normal serum that does not bind dinitrophenyl. J Exp Med. 1981 Nov 1;154(5):1442–1454. doi: 10.1084/jem.154.5.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eichmann K., Coutinho A., Melchers F. Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype-sensitized and anti-A5A idiotype-suppressed A/J mice. J Exp Med. 1977 Nov 1;146(5):1436–1449. doi: 10.1084/jem.146.5.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enghofer E., Glaudemans C. P., Bosma M. J. Immunoglobulins with different specificities have similar idiotypes. Mol Immunol. 1979 Dec;16(12):1103–1110. doi: 10.1016/0161-5890(79)90044-0. [DOI] [PubMed] [Google Scholar]
- Engvall E., Perlmann P. Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J Immunol. 1972 Jul;109(1):129–135. [PubMed] [Google Scholar]
- Estess P., Lamoyi E., Nisonoff A., Capra J. D. Structural studies on induced antibodies with defined idiotypic specificities. IX. Framework differences in the heavy- and light-chain-variable regions of monoclonal anti-p-azophenylarsonate antibodies from A/J mice differing with respect to a cross-reactive idiotype. J Exp Med. 1980 Apr 1;151(4):863–875. doi: 10.1084/jem.151.4.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galfrè G., Milstein C., Wright B. Rat x rat hybrid myelomas and a monoclonal anti-Fd portion of mouse IgG. Nature. 1979 Jan 11;277(5692):131–133. doi: 10.1038/277131a0. [DOI] [PubMed] [Google Scholar]
- Hart D. A., Wang A. L., Pawlak L. L., Nisonoff A. Suppression of idiotypic specificities in adult mice by administration of antiidiotypic antibody. J Exp Med. 1972 Jun 1;135(6):1293–1300. doi: 10.1084/jem.135.6.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henry C., Lucas A. The relation of idiotype expression to isotype and allotype in the anti-p-azobenzenearsonate response. Eur J Immunol. 1982 Mar;12(3):175–183. doi: 10.1002/eji.1830120302. [DOI] [PubMed] [Google Scholar]
- Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
- 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]
- Kohno Y., Berkower I., Minna J., Berzofsky J. A. Idiotypes of anti-myoglobin antibodies: shared idiotypes among monoclonal antibodies to distinct determinants of sperm whale myoglobin. J Immunol. 1982 Apr;128(4):1742–1748. [PubMed] [Google Scholar]
- Kresina T. F., Rosen S. M., Nisonoff A. Degree of heterogeneity of binding specificities of antibodies to the phenylarsonate group that share a common idiotype. Mol Immunol. 1982 Nov;19(11):1433–1439. doi: 10.1016/0161-5890(82)90190-0. [DOI] [PubMed] [Google Scholar]
- Laskin J. A., Gray A., Nisonoff A., Klinman N. R., Gottlieb P. D. Segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4600–4604. doi: 10.1073/pnas.74.10.4600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lieberman R., Potter M., Mushinski E. B., Humphrey W., Jr, Rudikoff S. Genetics of a new IgVH (T15 idiotype) marker in the mouse regulating natural antibody to phosphorylcholine. J Exp Med. 1974 Apr 1;139(4):983–1001. doi: 10.1084/jem.139.4.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshak-Rothstein A., Siekevitz M., Margolies M. N., Mudgett-Hunter M., Gefter M. L. Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1120–1124. doi: 10.1073/pnas.77.2.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metzger D. W., Miller A., Sercarz E. E. Sharing of an idiotypic marker by monoclonal antibodies specific for distinct regions of hen lysozyme. Nature. 1980 Oct 9;287(5782):540–542. doi: 10.1038/287540a0. [DOI] [PubMed] [Google Scholar]
- Miller G. G., Nadler P. I., Asano Y., Hodes R. J., Sachs D. H. Induction of idiotype-bearing, nuclease-specific helper T cells by in vivo treatment with anti-idiotype. J Exp Med. 1981 Jul 1;154(1):24–34. doi: 10.1084/jem.154.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelles M. J., Gill-Pazaris L. A., Nisonoff A. Monoclonal ant-idiotypic antibodies reactive with a highly conserved determinant on A/J serum anti-para-azophenylarsonate antibodies. J Exp Med. 1981 Dec 1;154(6):1752–1763. doi: 10.1084/jem.154.6.1752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- OLINS D. E., EDELMAN G. M. RECONSTITUTION OF 7S MOLECULES FROM L AND H POLYPEPTIDE CHAINS OF ANTIBODIES AND GAMMA-GLOBULINS. J Exp Med. 1964 May 1;119:789–815. doi: 10.1084/jem.119.5.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Owen F. L., Ju S. T., Nisonoff A. Presence on idiotype-specific suppressor T cells of receptors that interact with molecules bearing the idiotype. J Exp Med. 1977 Jun 1;145(6):1559–1566. doi: 10.1084/jem.145.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PORTER R. R. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J. 1959 Sep;73:119–126. doi: 10.1042/bj0730119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pawlak L. L., Hart D. A., Nisonoff A. Requirements for prolonged suppression of an idiotypic specificity in adult mice. J Exp Med. 1973 Jun 1;137(6):1442–1458. doi: 10.1084/jem.137.6.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rousseaux J., Bazin H. Rat immunoglobulins. Vet Immunol Immunopathol. 1979 Nov;1(1):61–78. doi: 10.1016/0165-2427(79)90008-4. [DOI] [PubMed] [Google Scholar]
- Sachs D. H., El-Gamil M., Miller G. Genetic control of the immune response to staphylococcal nuclease. XI. Effects of in vivo administration of anti-idiotypic antibodies. Eur J Immunol. 1981 Jun;11(6):509–516. doi: 10.1002/eji.1830110613. [DOI] [PubMed] [Google Scholar]
- Slack J., Der-Balian G. P., Nahm M., Davie J. M. Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency. J Exp Med. 1980 Apr 1;151(4):853–862. doi: 10.1084/jem.151.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TABACHNICK M., SOBOTKA H. Azoproteins. II. A spectrophotometric study of the coupling of diazotized arsanilic acid with proteins. J Biol Chem. 1960 Apr;235:1051–1054. [PubMed] [Google Scholar]
- Tung A. S., Ju S. T., Sato S., Nisonoff A. Production of large amounts of antibodies in individual mice. J Immunol. 1976 Mar;116(3):676–681. [PubMed] [Google Scholar]
- Tung A. S., Nisonoff A. Isolation from individual A/J mice of anti-rho-azophenylarsonate antibodies bearing a cross-reactive idiotype. J Exp Med. 1975 Jan 1;141(1):112–126. doi: 10.1084/jem.141.1.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Urbain J., Collignon C., Franssen J. D., Mariamé B., Léo O., Urbain-Vansanten G., Van de Walle P., Wikler M., Wuilmart C. Idiotypic networks and self-recognition in the immune system. Ann Immunol (Paris) 1979 Mar-Apr;130(2):281–291. [PubMed] [Google Scholar]
- Walker I. D., Morahan G. Monoclonal anti-azobenzenearsonate antibodies expressing the cross-reactive idiotype: immunochemical studies show that all idiotypic determinants reside on a single molecule. Scand J Immunol. 1981;13(5):433–440. doi: 10.1111/j.1365-3083.1981.tb00153.x. [DOI] [PubMed] [Google Scholar]
- Wysocki L. J., Sato V. L. The strain A anti-p-azophenylarsonate major cross-reactive idiotypic family includes members with no reactivity toward p-azophenylarsonate. Eur J Immunol. 1981 Oct;11(10):832–839. doi: 10.1002/eji.1830111016. [DOI] [PubMed] [Google Scholar]
