Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1979 Jun 1;149(6):1336–1348. doi: 10.1084/jem.149.6.1336

Hapten-specific T-cell responses to 4-hydroxy-3-nitrophenyl acetyl. I. Genetic control of delayed-type hypersensitivity by VH and I-A-region genes

PMCID: PMC2184899  PMID: 109567

Abstract

Hapten-specific delayed-type hypersensitivity (DTH) was induced in several strains of mice. (4-hydroxy-3-nitrophenyl)acetyl-bovine gamma globulin (NP-BGG)-primed mice which did not bear the Ig1b heavy-chain linkage group made a NP-specific DTH response when challenged with NP bovine serum albumin (BSA) and failed to respond to challenge with (4- hydroxy-5-iodo-3-nitrophenyl)acetyl-bovine serum albumin (NIP-BSA). Strains of NP-BGG-primed mice bearing the Ig1b allotype, including SJL, responded to challenges of either NP-BSA or NIP-BSA. F1 hybrids between a cross-reactive strain, C57BL/6, and two other noncross-reactive strains were cross-reactive. Genetic mapping of the NIP-cross-reactive DTH response localized the trait to the VH-region of the Ig1b heavy- chain linkage group. The fine-specificity pattern of the T-cell anti-NP response, and the genetic mapping of this trait, were analogous to the reported fine specificity and mapping data of the humoral heteroclitic anti-NP response. Adoptive transfer studies on the ability to transfer NP-specific DTH between various strain combinations showed that the T- cell donors and the recipient must have homology for at least the I-A subregion. Whenever NP-specific reactivity was transferred from a strain which cross-reactively responded to NIP, the recipient also responded to both NP and NIP. The implications of the control of NP- primed DTH-reactive populations of T cells by two distinct genetic regions, VH and H-2, were discussed.

Full Text

The Full Text of this article is available as a PDF (862.4 KB).

Selected References

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

  1. Askenase P. W., Hayden B. J., Gershon R. K. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses. J Exp Med. 1975 Mar 1;141(3):697–702. doi: 10.1084/jem.141.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bach B. A., Greene M. I., Benacerraf B., Nisonoff A. Mechanisms of regulation of cell-mediated immunity. IV. Azobenzenearsonate-specific suppressor factor(s) bear cross-reactive idiotypic determinants the expression of which is linked to the heavy-chain allotype linkage group of genes. J Exp Med. 1979 May 1;149(5):1084–1098. doi: 10.1084/jem.149.5.1084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevan M. J. Interaction antigens detected by cytotoxic T cells with the major histocompatibility complex as modifier. Nature. 1975 Jul 31;256(5516):419–421. doi: 10.1038/256419a0. [DOI] [PubMed] [Google Scholar]
  4. Binz H., Wigzell H. Antigen-binding, idiotypic T-lymphocyte receptors. Contemp Top Immunobiol. 1977;7:113–177. doi: 10.1007/978-1-4684-3054-7_4. [DOI] [PubMed] [Google Scholar]
  5. Burakoff S. J., Germain R. N., Dorf M. E., Benacerrah B. Inhibition of cell-mediated cytolysis of trinitrophenyl-derivatized target cells by alloantisera directed to the products of the K and D loci of the H-2 complex. Proc Natl Acad Sci U S A. 1976 Feb;73(2):625–629. doi: 10.1073/pnas.73.2.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cazenave P. A., Cavaillon J. M., Bona C. Idiotypic determinants of rabbit B- and T-derived lymphocytes. Immunol Rev. 1977;34:34–49. doi: 10.1111/j.1600-065x.1977.tb00367.x. [DOI] [PubMed] [Google Scholar]
  7. Cheung N. K., Scherr D. H., Heghinian K. M., Benacerraf B., Dorf M. E. Immune suppression in vivo with antigen-modified syngeneic cells. I. T-cell-mediated suppression to the terpolymer poly-(Glu, Lys, Phe)n. J Exp Med. 1978 Dec 1;148(6):1539–1549. doi: 10.1084/jem.148.6.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cosenza H., Augustin A., Julius M. H. Induction and characterization of "autologous" anti-isiotypic antibodies. Eur J Immunol. 1977 May;7(5):273–278. doi: 10.1002/eji.1830070506. [DOI] [PubMed] [Google Scholar]
  9. Cosenza H., Julius M. H., Augustin A. A. Idiotypes as variable region markers: analogies between receptors on phosphorylcholine-specific T and B lymphocytes. Immunol Rev. 1977;34:3–33. doi: 10.1111/j.1600-065x.1977.tb00366.x. [DOI] [PubMed] [Google Scholar]
  10. Debré P., Waltenbaugh C., Dorf M. E., Benacerraf B. Genetic control of specific immune suppression. IV. Responsiveness to the random copolymer L-glutamic acid50-L-tyrosine50 induced in BALB/c mice by cyclophosphamide. J Exp Med. 1976 Jul 1;144(1):277–281. doi: 10.1084/jem.144.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Geckeler W., Faversham J., Cohn M. On a regulatory gene controlling the expression of the murine lambda1 light chain. J Exp Med. 1978 Nov 1;148(5):1122–1136. doi: 10.1084/jem.148.5.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Germain R. N., Ju S. T., Kipps T. J., Benacerraf B., Dorf M. E. Shared idiotypic determinants on antibodies and T-cell-derived suppressor factor specific for the random terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10. J Exp Med. 1979 Mar 1;149(3):613–622. doi: 10.1084/jem.149.3.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hamaoka T., Yamaskita U., Takami T., Kitagawa M. The mechanism of tolerance induction in thymus-derived lymphocytes; I. intracellular inactivation of hapten-reactive helper T lymphocytes by hapten-nonimmunogenic copolymer of D-amino acids. J Exp Med. 1975 Jun 1;141(6):1308–1328. doi: 10.1084/jem.141.6.1308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hämmerling G. J., Black S. J., Berek C., Eichmann K., Rajewsky K. Idiotypic analysis of lymphocytes in vitro. II. Genetic control of T-helper cell responsiveness to anti-idiotypic antibody. J Exp Med. 1976 Apr 1;143(4):861–869. doi: 10.1084/jem.143.4.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Imanishi T., Mäkelä O. Inheritance of antibody specificity. I. Anti-(4-hydroxy-3-nitrophenyl)acetyl of the mouse primary response. J Exp Med. 1974 Dec 1;140(6):1498–1510. doi: 10.1084/jem.140.6.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jack R. S., Imanishi-Kari T., Rajewsky K. Idiotypic analysis of the response of C57BL/6 mice to the (4-hydroxy-3-nitrophenyl)acetyl group. Eur J Immunol. 1977 Aug;7(8):559–565. doi: 10.1002/eji.1830070813. [DOI] [PubMed] [Google Scholar]
  17. Karjalainen K., Mäkelä O. A mendelian idiotype is demonstrable in the heteroclitic anti-NP antibodies of the mouse. Eur J Immunol. 1978 Feb;8(2):105–111. doi: 10.1002/eji.1830080207. [DOI] [PubMed] [Google Scholar]
  18. Katz D. H., Hamaoka T., Dorf M. E., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. The H-2 gene complex determines successful physiologic lymphocyte interactions. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2624–2628. doi: 10.1073/pnas.70.9.2624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kontiainen S., Simpson E., Bohrer E., Beverley P. C., Herzenberg L. A., Fitzpatrick W. C., Vogt P., Torano A., McKenzie I. F., Feldmann M. T-cell lines producing antigen-specific suppressor factor. Nature. 1978 Aug 3;274(5670):477–480. doi: 10.1038/274477a0. [DOI] [PubMed] [Google Scholar]
  20. Krawinkel U., Cramer M., Berek C., Hämmerling G., Black S. J., Rajewsky K., Eichmann K. On the structure of the T-cell receptor for antigen. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):285–294. doi: 10.1101/sqb.1977.041.01.034. [DOI] [PubMed] [Google Scholar]
  21. Krawinkel U., Cramer M., Imanishi-Kari T., Jack R. S., Rajewsky K., Mäkelä O. Isolated hapten-binding receptors of sensitized lymphocytes. I. Receptors from nylon wool-enriched mouse T lymphocytes lack serological markers of immunoglobulin constant domains but express heavy chain variable portions. Eur J Immunol. 1977 Aug;7(8):566–573. doi: 10.1002/eji.1830070814. [DOI] [PubMed] [Google Scholar]
  22. Lagrange P. H., Mackaness G. B., Miller T. E. Potentiation of T-cell-mediated immunity by selective suppression of antibody formation with cyclophosphamide. J Exp Med. 1974 Jun 1;139(6):1529–1539. doi: 10.1084/jem.139.6.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5095–5098. doi: 10.1073/pnas.72.12.5095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. Role of major histocompatibility complex gene products in delayed-type hypersensitivity. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2486–2490. doi: 10.1073/pnas.73.7.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mäkelä O., Karjalainen K. Inherited immunoglobulin idiotypes of the mouse. Immunol Rev. 1977;34:119–138. doi: 10.1111/j.1600-065x.1977.tb00370.x. [DOI] [PubMed] [Google Scholar]
  27. Rajewsky K., Eichmann K. Antigen receptors of T helper cells. Contemp Top Immunobiol. 1977;7:69–112. doi: 10.1007/978-1-4684-3054-7_3. [DOI] [PubMed] [Google Scholar]
  28. Ramseier H., Aguet M., Lindenmann J. Similarity of idiotypic determinants of T-and B-lymphocyte receptors for alloantigens. Immunol Rev. 1977;34:50–88. doi: 10.1111/j.1600-065x.1977.tb00368.x. [DOI] [PubMed] [Google Scholar]
  29. Riblet R., Weigert M., Mäkelä O. Genetics of mouse antibodies. II. Recombination between VH genes and allotype. Eur J Immunol. 1975 Nov;5(11):778–781. doi: 10.1002/eji.1830051110. [DOI] [PubMed] [Google Scholar]
  30. Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]
  31. Turk J. L., Parker D., Poulter L. W. Functional aspects of the selective depletion of lymphoid tissue by cyclophosphamide. Immunology. 1972 Oct;23(4):493–501. [PMC free article] [PubMed] [Google Scholar]
  32. Yamashita U., Kitagawa M. Induction of anti-hapten antibody response by hapten-isologous carrier conjugate. I. Development of hapten-reactive helper cells by hapten-isologous carrier. Cell Immunol. 1974 Nov;14(2):182–192. doi: 10.1016/0008-8749(74)90204-4. [DOI] [PubMed] [Google Scholar]
  33. Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]
  34. Zinkernagel R. M. Thymus and lymphohemopoietic cells: their role in T cell maturation in selection of T cells' H-2-restriction-specificity and in H-2 linked Ir gene control. Immunol Rev. 1978;42:224–270. doi: 10.1111/j.1600-065x.1978.tb00264.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES