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. 1976 Aug;73(8):2862–2866. doi: 10.1073/pnas.73.8.2862

Determinants of antigenic molecules responsible for genetically controlled regulation of immune responses.

M Schwartz, C Waltenbaugh, M Dorf, R Cesla, M Sela, B Benacerraf
PMCID: PMC430778  PMID: 60762

Abstract

The ability of mice bearing the H-2S haplotype to develop helper responses to the random copolymer of Glu,Ala while they developed suppressor responses to the terpolymer of Glu,Ala,Tyr suggested the crucial role of tyrosine in these peptides. On the basis of various considerations, it was postulated that many of the tyrosine residues in Glu,Ala,Tyr would be localized at the NH2-terminal end of the molecule. To verify this hypothesis, a block terpolymer composed of a short sequence of homopolymer tyrosine covalently bound to the random copolymer of Glu,Ala was synthesized. The present studies, using this block terpolymer, demonstrated that the chemical determinants stimulating helper and suppressor responses are distinct and can be present simultaneously in the same molecule. Thus, addition of COOH-terminal tyrosine residues to the Glu,Ala polypeptide converted this immunogenic molecule to an immunosuppressive molecule in mice bearing the H-2S haplotype. The mechanism by which these short sequences of tyrosine influence H-2-linked immune responses remains to be determined.

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Selected References

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

  1. Benacerraf B., Kapp J. A., Debré P., Pierce C. W., de la Croix F. The stimulation of specific suppressor T cells in genetic non-responder mice by linear random copolymers of L-amino acids. Transplant Rev. 1975;26:21–38. doi: 10.1111/j.1600-065x.1975.tb00173.x. [DOI] [PubMed] [Google Scholar]
  2. Benacerraf B., Katz D. H. The histocompatibility-linked immune response genes. Adv Cancer Res. 1975;21:121–173. doi: 10.1016/s0065-230x(08)60972-0. [DOI] [PubMed] [Google Scholar]
  3. Benacerraf B., McDevitt H. O. Histocompatibility-linked immune response genes. Science. 1972 Jan 21;175(4019):273–279. doi: 10.1126/science.175.4019.273. [DOI] [PubMed] [Google Scholar]
  4. Debré P., Kapp J. A., Dorf M. E., Benacerraf B. Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT). J Exp Med. 1975 Dec 1;142(6):1447–1454. doi: 10.1084/jem.142.6.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
  6. Dorf M. E., Balner H., de Groot M. L., Benacerraf B. Histocompatibility-linked immune-response genes in the rhesus monkey. Transplant Proc. 1974 Jun;6(2):119–123. [PubMed] [Google Scholar]
  7. Dorf M. E., Benacerraf B. Complementation of H-2-linked Ir genes in the mouse. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3671–3675. doi: 10.1073/pnas.72.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ellman L., Green I., Martin W. J., Benacerraf B. Linkage between the poly-L-lysine gene and the locus controlling the major histocompatibility antigens in strain 2 guinea pigs. Proc Natl Acad Sci U S A. 1970 Jun;66(2):322–328. doi: 10.1073/pnas.66.2.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Erb P., Feldmann M. The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. J Exp Med. 1975 Aug 1;142(2):460–472. doi: 10.1084/jem.142.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Green I., Paul W. E., Benacerraf B. The behavior of hapten-poly-L-lysine conjugates as complete antigens in genetic responder and as haptens in nonresponder guinea pigs. J Exp Med. 1966 May 1;123(5):859–879. doi: 10.1084/jem.123.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Günther E., Rüde E., Stark O. Antibody response in rats to the synthetic polypeptide (T,G)-A--L genetically linked to the major histocompatibility system. Eur J Immunol. 1972 Apr;2(2):151–155. doi: 10.1002/eji.1830020211. [DOI] [PubMed] [Google Scholar]
  12. Hill S. W., Sercarz E. E. Fine specificity of the H-2 linked immune response gene for the gallinaceous lysozymes. Eur J Immunol. 1975 May;5(5):317–324. doi: 10.1002/eji.1830050506. [DOI] [PubMed] [Google Scholar]
  13. KATCHALSKI E., SELA M. Synthesis and chemical properties of poly-alpha-amino acids. Adv Protein Chem. 1958;13:243–492. doi: 10.1016/s0065-3233(08)60600-2. [DOI] [PubMed] [Google Scholar]
  14. Kapp J. A., Pierce C. W., Benacerraf B. Genetic control of immune responses in vitro. 3. Tolerogenic properties of the terpolymer L-glutamic acid 60-L-alanine30-L-tyrosine10 (GAT) for spleen cells from nonresponder (H-2s and H-2q) mice. J Exp Med. 1974 Jul 1;140(1):172–184. doi: 10.1084/jem.140.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kapp J. A., Pierce C. W., Benacerraf B. Genetic control of immune responses in vitro. I. Development of primary and secondary plaque-forming cell responses to the random terpolymer 1-glutamic acid 60-1-alanine30-1-tyrosine10 (GAT) by mouse spleen cells in vitro. J Exp Med. 1973 Nov 1;138(5):1107–1120. doi: 10.1084/jem.138.5.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kapp J. A., Pierce C. W., Schlossman S., Benacerraf B. Genetic control of immune responses in vitro. V. Stimulation of suppressor T cells in nonresponder mice by the terpolymer L-glutamic acid 60-L-alanine 30-L-tyrosine 10 (GAT). J Exp Med. 1974 Sep 1;140(3):648–659. doi: 10.1084/jem.140.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Keck K. Ir-gene control of immunogenicity of insulin and A-chain loop as a carrier determinant. Nature. 1975 Mar 6;254(5495):78–79. doi: 10.1038/254078a0. [DOI] [PubMed] [Google Scholar]
  18. Merryman C. F., Maurer P. H. Genetic control of immune response against random copolymers of glutamic acid and alanine (GA) and tyrosine (GT) in inbred mice. J Immunol. 1976 Mar;116(3):739–742. [PubMed] [Google Scholar]
  19. 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]
  20. Pierce C. W., Johnson B. M., Gershon H. E., Asofsky R. Immune responses in vitro. 3. Development of primary gamma-M, gamma-G, and gamma-A plaque-forming cell responses in mouse spleen cell cultures stimulated with heterologous erythrocytes. J Exp Med. 1971 Aug 1;134(2):395–416. doi: 10.1084/jem.134.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sela M. Immunological studies with synthetic polypeptides. Adv Immunol. 1966;5:29–129. doi: 10.1016/s0065-2776(08)60272-2. [DOI] [PubMed] [Google Scholar]

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