Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1980 Feb 1;151(2):265–274. doi: 10.1084/jem.151.2.265

Genetic regulation of delayed-type hypersensitivity responses to poly(LTyr,LGu)-poly(DLAla)--poly(LLys). I. Expression of the genetic defect at two phases of the immune process

PMCID: PMC2185780  PMID: 6766173

Abstract

Delayed-type hypersensitivity (DTH) responses served in this study as an experimental model for the analysis of genetic regulations of T-cell responses. Educated irradiated cells from H-2b mice mediated responses in syngeneic recipients, whereas mice of the a, d, f, k, and s haplotypes were nonresponders to poly(LTyr,LGlu)-poly(DLAla)-- poly(LLys)[(T,G)-A--L]. These results suggest that cell-mediated immune responsiveness to (T,G)-A--L is linked to the H-2 complex, as was shown for humoral responses. Educated irradiated T cells of F1 hybrids between high and low responders mediated DTH responses, which indicates that the gene(s) controlling the DTH responses is dominant. To analyze the genetic defect in DTH responses to (T,G)-A--L, we separated the T- cell activation phase from the effector phase that was determined in recipient mice. Two types of nonresponders were observed: (a) When lymphocytes of the a or k haplotypes were educated in a syngeneic environment and then transferred into hybrids between the parental (nonresponder x responder) F1 recipients, DTH responses could have been manifested. (b) On the other hand, no DTH responses could be mediated by transferring educated cells of the H-2s or H-2f origin into the appropriate F1 recipients. In addition, irradiated F1 cells that had been activated to (T,G)-A--L could not mediate DTH responses in both types of nonresponder recipients. These results suggest that T cells of H-2k or H-2a mice can be activated to generate DTH responses to (T,G)-A- -L and that the defect in these mouse strains is expressed in another cell population needed for the manifestation of the DTH reaction in the recipient mice. In contrast, T cells of H-2s and H-2f origin cannot be activated to (T,G)-A--L and, thus, fail to manifest DTH responses.

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. 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]
  2. Davis S., Shearer G. M., Mozes E., Sela M. Genetic control of the murine cell-mediated immune response in vivo. II. H-2 linked responsiveness to the synthetic polypeptide poly(Tyr,Glu)-poly(DL-Ala)--poly(Lys). J Immunol. 1975 Dec;115(6):1530–1532. [PubMed] [Google Scholar]
  3. Eshhar Z., Strassmann G., Waks T., Mozes E. In vitro and in vivo induction of effector T cells mediating DTH responses to a protein and a synthetic polypeptide antigen. Cell Immunol. 1979 Oct;47(2):378–389. doi: 10.1016/0008-8749(79)90347-2. [DOI] [PubMed] [Google Scholar]
  4. Howie S., Feldman M. In vitro studies on H-2-linked unresponsiveness to synthetic polypeptides. III. Production of an antigen-specific T helper cell factor to (T,G)-A--L. Eur J Immunol. 1977 Jul;7(7):417–421. doi: 10.1002/eji.1830070703. [DOI] [PubMed] [Google Scholar]
  5. Lichtenberg L., Mozes E., Shearer G. M., Sela M. The role of thymus cells in the immune response to poly(Tyr, Glu)-polyD L Ala--polyLys as a function of the genetic constitution of the mouse strain. Eur J Immunol. 1974 Jun;4(6):430–434. doi: 10.1002/eji.1830040609. [DOI] [PubMed] [Google Scholar]
  6. Marrack P., Kappler J. W. The role of H-2-linked genes in helper T-cell function. III. Expression of immune response genes for trinitrophenyl conjugates of poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in B cells and macrophages. J Exp Med. 1978 Jun 1;147(6):1596–1610. doi: 10.1084/jem.147.6.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Marrack P., Kappler J. W. The role of H-2-linked genes in helper T-cell function. VI. Expression of Ir genes by helper T cells. J Exp Med. 1979 Mar 1;149(3):780–785. doi: 10.1084/jem.149.3.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McDevitt H. O., Benacerraf B. Genetic control of specific immune responses. Adv Immunol. 1969;11:31–74. doi: 10.1016/s0065-2776(08)60477-0. [DOI] [PubMed] [Google Scholar]
  9. McDevitt H. O., Deak B. D., Shreffler D. C., Klein J., Stimpfling J. H., Snell G. D. Genetic control of the immune response. Mapping of the Ir-1 locus. J Exp Med. 1972 Jun 1;135(6):1259–1278. doi: 10.1084/jem.135.6.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McDevitt H. O., Sela M. Genetic control of the antibody response. I. Demonstration of determinant-specific differences in response to synthetic polypeptide antigens in two strains of inbred mice. J Exp Med. 1965 Sep 1;122(3):517–531. doi: 10.1084/jem.122.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McDevitt H. O., Tyan M. L. Genetic control of the antibody response in inbred mice. Transfer of response by spleen cells and linkage to the major histocompatibility (H-2) locus. J Exp Med. 1968 Jul 1;128(1):1–11. [PMC free article] [PubMed] [Google Scholar]
  12. Miller J. F., Vadas M. A., Whitelaw A., Gamble J., Bernard C. Histocompatibility linked immune responsiveness and restrictions imposed on sensitized lymphocytes. J Exp Med. 1977 Jun 1;145(6):1623–1628. doi: 10.1084/jem.145.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mozes E., Isac R., Taussig M. J. Antigen-specific T-cell factors in the genetic control of the immune response to poly(Tyr,Glu)-polyDLAla--polyLys. Evidence for T- and B-cell defects in SJL mice. J Exp Med. 1975 Mar 1;141(3):703–707. doi: 10.1084/jem.141.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mozes E., McDevitt H. O., Jaton J. C., Sela M. The nature of the antigenic determinant in a genetic control of the antibody response. J Exp Med. 1969 Sep 1;130(3):493–504. doi: 10.1084/jem.130.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mozes E., Shearer G. M. Genetic control of immune responses. Curr Top Microbiol Immunol. 1972;59:167–200. doi: 10.1007/978-3-642-65444-2_6. [DOI] [PubMed] [Google Scholar]
  16. Munro A. J., Taussig M. J. Two genes in the major histocompatibility complex control immune response. Nature. 1975 Jul 10;256(5513):103–106. doi: 10.1038/256103a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Schwartz R. H., Horton C. L., Paul W. E. T-lymphocyte-enriched murine peritoneal exudate cells. IV. Genetic control of cross-stimulation at the T-cell level. J Exp Med. 1977 Feb 1;145(2):327–343. doi: 10.1084/jem.145.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sela M. Antigenicity: some molecular aspects. Science. 1969 Dec 12;166(3911):1365–1374. doi: 10.1126/science.166.3911.1365. [DOI] [PubMed] [Google Scholar]
  20. Singer A., Cowing C., Hathcock K. S., Dickler H. B., Hodes R. J. Cellular and genetic control of antibody responses in vitro. III. Immune response gene regulation of accessory cell function. J Exp Med. 1978 Jun 1;147(6):1611–1620. doi: 10.1084/jem.147.6.1611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Taussig J., Mozes E., Isac R. Antigen-specific thymus cell factors in the genetic control of the immune response to poly-(tyrosyl, glutamyl)-poly-D, L-alanyl--poly-lysyl. J Exp Med. 1974 Aug 1;140(2):301–312. doi: 10.1084/jem.140.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vadas M. A., Miller J. F., Gamble J., Whitelaw A. A radioisotopic method to measure delayed type hypersensitivity in the mouse. I. Studies in sensitized and normal mice. Int Arch Allergy Appl Immunol. 1975;49(5):670–692. doi: 10.1159/000231449. [DOI] [PubMed] [Google Scholar]

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

RESOURCES