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. 1979 Oct;76(10):5286–5288. doi: 10.1073/pnas.76.10.5286

Change in specificity of antibodies to a random synthetic branched polypeptide in mice tolerant to its ordered analogs

Michal Schwartz 1, Behnaz Parhami 1, Edna Mozes 1, Michael Sela 1
PMCID: PMC413126  PMID: 291946

Abstract

The crossreactivity between the random synthetic polypeptide antigen, (Tyr,Glu)-poly(DLAla)- -poly(Lys), and its ordered sequence analogs, (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) and (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys), has been studied on the level of tolerance induction. Induction of tolerance to the random (Tyr,Glu)-poly(DLAla)- -poly(Lys) affected the response of the tolerant mice to the homologous antigen as well as to (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys), which was shown previously to represent the major determinant of (Tyr,Glu)-poly(DLAla)- -poly(Lys). In contrast, these mice responded with high antibody titers to the hardly crossreacting (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys). Mice tolerant to the ordered peptide antigen (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys) did not respond to the homologous polypeptide; however, their immune response to either (Tyr-Glu)-poly(DLAla)- -poly(Lys) or (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) was not affected. Mice that were tolerant to (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) responded well to (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys). Furthermore, these mice produced high antibody titers after immunization with the random (Tyr,Glu)-poly(DLAla)- -poly(Lys). However, the antibodies produced were not specific to the major determinant of (Tyr,Glu)-poly(DLAla)- -poly(Lys), namely, Tyr-Tyr-Glu-Glu, but were directed to minor determinants of the random polypeptide, including Tyr-Glu-Tyr-Glu, which are not immunopotent when nontolerant mice are immunized with (Tyr,Glu)-poly(DLAla)- -poly(Lys). Thus, whereas antigenic specificity reflects itself also at the level of tolerance induction, the animals that had been made tolerant are capable of responding to previously silent antigenic determinants.

Keywords: synthetic antigens, tolerance induction, antibody specificity, antigenic determinants

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Selected References

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

  1. BROWN R. K., TRZPIS M. A., SELA M., ANFINSEN C. B. STUDIES ON THE ANTIGENIC STRUCTURE OF RIBONUCLEASE. IV. POLYALANYL RIBONUCLEASE. J Biol Chem. 1963 Dec;238:3876–3883. [PubMed] [Google Scholar]
  2. Bauminger S., Schechter I., Sela M. Specificity of immunological tolerance to poly-DL-aalanyl proteins. Immunochemistry. 1967 May;4(3):169–181. doi: 10.1016/0019-2791(67)90126-7. [DOI] [PubMed] [Google Scholar]
  3. Bonavida B., Mozes E., Shearer G. M., Sela M. Immunological unresponsiveness induced in adult mice to synthetic polypeptides built on multichain polyproline and multichain polyalanine. Immunochemistry. 1974 Jul;11(7):347–353. doi: 10.1016/0019-2791(74)90187-6. [DOI] [PubMed] [Google Scholar]
  4. Klinman N. R., Pickard A. R., Sigal N. H., Gearhart P. J., Metcalf E. S., Pierce S. K. Assessing B cell diversification by antigen receptor and precursor cell analysis. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):489–502. [PubMed] [Google Scholar]
  5. Mozes E., Schwartz M., Sela M. Antibody response of inbred mouse strains to ordered tetrapeptides of tyrosine and glutamic acid attached to multichain polyalanine or polyproline. Tyr-Tyr-Glu-Glu is a major determinant of the random poly-(Tyr, Glu)-polyDLAla--polyLys. J Exp Med. 1974 Aug 1;140(2):349–355. doi: 10.1084/jem.140.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mozes E., Sela M., Taussig M. J. Tolerance to thymus-independent antigens. Characteristics of induction of tolerance to thymus-independent synthetic polypeptides. Immunology. 1974 Oct;27(4):641–646. [PMC free article] [PubMed] [Google Scholar]
  7. Ramachandran J., Berger A., Katchalski E. Synthesis and physicochemical properties in aqueous solution of the sequential polypeptide poly(Tyr-Ala-Glu). Biopolymers. 1971 Oct;10(10):1829–1851. doi: 10.1002/bip.360101007. [DOI] [PubMed] [Google Scholar]
  8. Ruben T. J., Chiller J. M., Weigle W. O. The cellular basis of cross-tolerance. J Immunol. 1973 Sep;111(3):805–810. [PubMed] [Google Scholar]
  9. SELA M., FUCHS S., ARNON R. Studies on the chemical basis of the antigenicity of proteins. 5. Synthesis, characterization and immunogenicity of some multichain and linear polypeptides containing tyrosine. Biochem J. 1962 Oct;85:223–235. doi: 10.1042/bj0850223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Schwartz M., Geiger B., Hooghe R., Bar-Eli M., Gallily R., Mozes E., Sela M. The mode of interaction with macrophages of two ordered synthetic polypeptides which differ in their thymus dependency. Immunology. 1978 Nov;35(5):849–855. [PMC free article] [PubMed] [Google Scholar]
  11. Schwartz M., Hooghe R. J., Mozes E., Sela M. Role of antigenic structure in cell to cell cooperation. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4184–4186. doi: 10.1073/pnas.73.11.4184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Shearer G. M., Mozes E., Sela M. Cellular basis of the genetic control of immune responses to synthetic polypeptides. II. Frequency of immunocompetent precursors specific for two distinct regions within (Phe, G)-Pro--L, a synthetic polypeptide derived from multichain polyproline, in inbred mouse strains. J Exp Med. 1971 Feb 1;133(2):216–230. doi: 10.1084/jem.133.2.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Taussig M. J. Antigenic competition. Curr Top Microbiol Immunol. 1973;60:125–174. doi: 10.1007/978-3-642-65502-9_4. [DOI] [PubMed] [Google Scholar]
  14. Taussig M. J., Lachmann P. J. Studies on antigenic competition. II. Abolition of antigenic competition by antibody against or tolerance to the dominant antigen: a model for antigenic competition. Immunology. 1972 Feb;22(2):185–197. [PMC free article] [PubMed] [Google Scholar]
  15. Taussig M. J., Mozes E., Shearer G. M., Sela M. Cooperation of antigenic determinants in intact mice and interference by antigenic competition. Eur J Immunol. 1972 Dec;2(6):577–581. doi: 10.1002/eji.1830020619. [DOI] [PubMed] [Google Scholar]
  16. Taussig M. J. Studies on antigenic competition. I. Antigenic competition between the Fc and Fab fragments of rabbit IgG in mice. Immunology. 1971 Jul;21(1):51–60. [PMC free article] [PubMed] [Google Scholar]

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