Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Feb 1;159(2):479–494. doi: 10.1084/jem.159.2.479

Activation specificity of arsonate-reactive T cell clones. Structural requirements for hapten recognition and comparison with monoclonal antibodies

PMCID: PMC2187238  PMID: 6198431

Abstract

We describe clones of hapten-specific inducer T cells from (BALB/c X A/J)F1 mice that respond to the p-azobenzenearsonate hapten conjugated to carrier proteins or directly conjugated to antigen-presenting cells. Some of the clones are also activated by haptens structurally related to arsonate. All activating analogues are recognized by each clone in association with the same major histocompatibility complex (MHC) protein as is arsonate. Weakly activating and nonactivating analogues are immunogenic in D2.GD amd (BALB/c X A/J)F1 mice, since they can effectively activate primed lymph node cells or long-term hapten- reactive cell lines. Hence the specificities of these clones may reflect their intrinsic recognition of arsonate and its analogues, rather than more efficient presentation of certain analogues than of others by antigen-presenting cells, or differential recognition of associated MHC epitopes by the clones. We compare the activation specificities of the clones with the binding specificities of monoclonal antibodies to arsonate, and discuss structural features of the analogues that may be important for activation and binding. Our results suggest that a site (or subsite) on arsonate-reactive T cell clones may interact directly with hapten, and may be experimentally separable from the site (or subsite) for MHC determinants.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Alkan S. S., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response: the capacity of L-tyrosine-azobenzenearsonate to serve as a carrier for a macromolecular hapten. J Immunol. 1971 Aug;107(2):353–358. [PubMed] [Google Scholar]
  2. Alkan S. S., Williams E. B., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response. Humoral and cellular immune responses to small mono- and bifunctional antigen molecules. J Exp Med. 1972 Jun 1;135(6):1228–1246. doi: 10.1084/jem.135.6.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  4. Clayberger C., Dekruyff R. H., Aisenberg J., Cantor H. Hapten-reactive inducer T cells. I. Definition of two classes of hapten-specific inducer cells. J Exp Med. 1983 Jun 1;157(6):1906–1919. doi: 10.1084/jem.157.6.1906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Freedman M. H., Grossberg A. L., Pressman D. Evidence for ammonium and guanidinium groups in the combining sites of anti-p-azobenzenearsonate antibodies--separation of two different populations of antibody molecules. J Biol Chem. 1968 Dec 10;243(23):6186–6195. [PubMed] [Google Scholar]
  6. Freedman M. H., Grossberg A. L., Pressman D. The effects of complete modification of amino groups on the antibody activity of antihapten antibodies. Reversible inactivation with maleic anhydride. Biochemistry. 1968 May;7(5):1941–1950. doi: 10.1021/bi00845a044. [DOI] [PubMed] [Google Scholar]
  7. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  8. Hanna N., Leskowitz S. Structural requirements for in vivo and in vitro immunogenicity in hapten-specific delayed hypersensitivity. Cell Immunol. 1973 May;7(2):189–197. doi: 10.1016/0008-8749(73)90241-4. [DOI] [PubMed] [Google Scholar]
  9. Haselkorn D., Friedman S., Givol D., Pecht I. Kinetic mapping of the antibody combining site by chemical relaxation spectrometry. Biochemistry. 1974 May 7;13(10):2210–2222. doi: 10.1021/bi00707a030. [DOI] [PubMed] [Google Scholar]
  10. Heber-Katz E., Schwartz R. H., Matis L. A., Hannum C., Fairwell T., Appella E., Hansburg D. Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation. J Exp Med. 1982 Apr 1;155(4):1086–1099. doi: 10.1084/jem.155.4.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hertel-Wulff B., Goodman J. W., Fathman C. G., Lewis G. K. Arsonate-specific murine T cell clones. I. Genetic control and antigen specificity. J Exp Med. 1983 Mar 1;157(3):987–997. doi: 10.1084/jem.157.3.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ho M. K., Guidotti G. A membrane protein from human erythrocytes involved in anion exchange. J Biol Chem. 1975 Jan 25;250(2):675–683. [PubMed] [Google Scholar]
  13. Janeway C. A., Jr The specificity of T lymphocyte responses to chemically defined antigens. Transplant Rev. 1976;29:164–188. doi: 10.1111/j.1600-065x.1976.tb00201.x. [DOI] [PubMed] [Google Scholar]
  14. Jensenius J. C., Williams A. F. The T lymphocyte antigen receptor--paradigm lost. Nature. 1982 Dec 16;300(5893):583–588. doi: 10.1038/300583a0. [DOI] [PubMed] [Google Scholar]
  15. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  16. 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]
  17. Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lamoyi E., Estess P., Capra J. D., Nisonoff A. Heterogeneity of an intrastrain cross-reactive idiotype associated with anti-p-azophenylarsonate antibodies of A/J mice. J Immunol. 1980 Jun;124(6):2834–2840. [PubMed] [Google Scholar]
  19. Leskowitz S., Jones V. E., Zak S. J. Immunochemical study of antigenic specificity in delayed hypersensitivity. V. Immunization with monovalent low molecular weight conjugates. J Exp Med. 1966 Feb 1;123(2):229–237. doi: 10.1084/jem.123.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pohlit H., Haas W., von Boehmer H. Cytotoxic T cell responses to haptenated cells. I. Primary, secondary and long-term cultures. Eur J Immunol. 1979 Sep;9(9):681–690. doi: 10.1002/eji.1830090905. [DOI] [PubMed] [Google Scholar]
  21. Rao A., Allard W. J., Hogan P. G., Rosenson R. S., Cantor H. Alloreactive T-cell clones. Ly phenotypes predict both function and specificity for major histocompatibility complex products. Immunogenetics. 1983;17(2):147–165. doi: 10.1007/BF00364755. [DOI] [PubMed] [Google Scholar]
  22. Rao A., Faas S. J., Miller L. J., Riback P. S., Cantor H. Lysis of inducer T cell clones by activated macrophages and macrophage-like cell lines. J Exp Med. 1983 Oct 1;158(4):1243–1258. doi: 10.1084/jem.158.4.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rao A., Martin P., Reithmeier R. A., Cantley L. C. Location of the stilbenedisulfonate binding site of the human erythrocyte anion-exchange system by resonance energy transfer. Biochemistry. 1979 Oct 16;18(21):4505–4516. doi: 10.1021/bi00588a008. [DOI] [PubMed] [Google Scholar]
  24. Rothstein T. L., Margolies M. N., Gefter M. L., Marshak-Rothstein A. Fine specificity of idiotope suppression in the A/J anti-azophenylarsonate response. J Exp Med. 1983 Feb 1;157(2):795–800. doi: 10.1084/jem.157.2.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. SCHLOSSMAN S. F., KABAT E. A. Specific fractionation of a population of antidextran molecules with combining sites of various sizes. J Exp Med. 1962 Oct 1;116:535–552. doi: 10.1084/jem.116.4.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schechter I. Mapping of the combining sites of antibodies specific for poly-L-alanine determinants. Nature. 1970 Nov 14;228(5272):639–641. doi: 10.1038/228639a0. [DOI] [PubMed] [Google Scholar]
  27. Schlossman S. F. Antigen recognition: the specificity of T cells involved in the cellular immune response. Transplant Rev. 1972;10:97–111. doi: 10.1111/j.1600-065x.1972.tb01540.x. [DOI] [PubMed] [Google Scholar]
  28. Schwartz R. H., Yano A., Paul W. E. Interaction between antigen-presenting cells and primed T lymphocytes: an assessment of Ir gene expression in the antigen-presenting cell. Immunol Rev. 1978;40:153–180. doi: 10.1111/j.1600-065x.1978.tb00405.x. [DOI] [PubMed] [Google Scholar]
  29. Sherman L. A., Burakoff S. J., Benacerraf B. The induction of cytolytic T lymphocytes with specificity for p-azophenylarsonate coupled syngeneic cells. J Immunol. 1978 Oct;121(4):1432–1436. [PubMed] [Google Scholar]
  30. Sredni B., Tse H. Y., Chen C., Schwartz R. H. Antigen-specific clones of proliferating T lymphocytes. I. Methodology, specificity, and MHC restriction. J Immunol. 1981 Jan;126(1):341–347. [PubMed] [Google Scholar]
  31. TABACHNICK M., SOBOTKA H. Azoproteins. I. Spectrophotometric studies of amino acid azo derivatives. J Biol Chem. 1959 Jul;234(7):1726–1730. [PubMed] [Google Scholar]
  32. 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]
  33. Velick S. F., Parker C. W., Eisen H. N. EXCITATION ENERGY TRANSFER AND THE QUANTITATIVE STUDY OF THE ANTIBODY HAPTEN REACTION. Proc Natl Acad Sci U S A. 1960 Nov;46(11):1470–1482. doi: 10.1073/pnas.46.11.1470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Woodland R., Cantor H. Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol. 1978 Aug;8(8):600–606. doi: 10.1002/eji.1830080812. [DOI] [PubMed] [Google Scholar]
  35. Yokota S., Lafuse W. P., McCormick J. F., David C. S. Detection of hybrid (combinatorial) Ia antigens using parent anti-F1 sera. J Immunol. 1981 Jan;126(1):371–374. [PubMed] [Google Scholar]

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

RESOURCES