Advertisement

Suppressor T Cells Induced in Vivo by Tolerogenic Conjugates of a Given Antigen and Monomethoxypolyethylene Glycol Downregulate Antibody Formation Also to a Second Antigen, if the Latter is Presented as a Covalent Adduct with the Former

  • Alec H. Sehon
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 303)

Abstract

Recent results of studies employing tolerogenic monomethoxypolyethylene glycol (mPEG) conjugates of antigens are briefly reviewed. Administration of antigen(mPEG)n conjugates into mice induced antigen specific suppressor T (Ts) cells, from which a suppressor factor (TsF) was extracted. These Ts cells were cloned and shown to be Thyl.2+, CD3+, CD4, CD5, CD8+ and to express the αβ heterodimer of conventional T cell receptors (TCR). The TsF of a clone of OVA-specific Ts cells shared the epitopes of the α and β chains of TCR, whereas the TsF of T cells of an HIgG-specific clone shared only the epitope of the α chains of TCR; OVA and HIgG represent ovalbumin and human monoclonal (myeloma) IgG. These studies have provided evidence for the phenomenon of “linked immunological suppression” which may be summarized by the statement “Ts cells specific for an epitope of a given antigen, AgA, suppress the antibody response to an unrelated antigen, AgB, only if the latter is presented in the form of a covalent adduct, AgA-AgB, to the immune system of the animal pretolerized with AgA (mPEG)n, but not if AgB is presented as a mixture with AgA.

Keywords

Antibody Response Antigen Present Cell Covalent Adduct ELISA Titre Syngeneic Recipient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Atassi, M. Z., Zouhair, M., Yoshioka, M., and Bixler, Y. S., Jr., 1989, T cells specific for α−β interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing, Proc. Natl, Acad, Sci. U.S.A., 86:6729.CrossRefGoogle Scholar
  2. Buzi, F., Buchanan, C.R., Morrell, D.J., and Preece, M.A., 1989, Antigenicity and efficacy of authentic sequence recombinant human growth hormone (somatropin): First-year experience in the United Kingdom, Clin. Endocrinology. 30:531.CrossRefGoogle Scholar
  3. Cruse, J. M. and Lewis, R. E., Jr., eds., 1989, “Therapy of autoimunne diseases,” Karger, Basel.Google Scholar
  4. Diamantstein, T. and Osawa, H., 1986, The interleukin-2 receptor, its physiology and a new approach to a selective immunosuppressive therapy by anti-interleukin-2 receptor monoclonal antibodies, in: “Immunol. Rev.,” 92:5, G. Möller, ed., Munksgaard, Copenhagen.Google Scholar
  5. Frankel, A. E., 1988, “Immunotoxins,” Kluwer Academic Publishers, Boston.Google Scholar
  6. Katre, N. V., 1990, Immunogenicity of recombinant IL-2 modified by covalent attachment of polyethylene glycol, J. Immunol., 144:144.Google Scholar
  7. Maiti, P. K., Lang, G. M., and Sehon, A. H., 1988, Tolerogenic conjugates of xenogeneic monoclonal antibodies with monomethoxy-polyethylene glycol. I. Induction of long-lasting tolerance to xenogeneic monoclonal antibodies, Int. J. Cancer. 3:17.CrossRefGoogle Scholar
  8. Mitchison, N. A., 1989, Suppression of the response to murine alloantigens: Four-cell-type clusters, function-flipping and idiosyncratic responses, in: “Antigenic determinants and immune regulation”, Chem. Immunol., 46:157, E.Sercarz, ed., Karger,Basel.CrossRefGoogle Scholar
  9. Mokashi, S., Holford-Strevens, V., Sterrantino, G., Jackson, C-J. C., and Sehon, A.H., 1989, Down-regulation of secondary in vitro antibody responses by suppressor T cells of mice treated with a tolerogenic conjugate of ovalbumin and monomethoxypolyethylene glycol, OVA(mPEG)13, Immunol. Lett., 23:95.PubMedCrossRefGoogle Scholar
  10. Rock, K.L., Gamble, S., and Rothstein, L., 1990, Presentation of exogeneous antigen with class I major histocompatibility complex molecules, Science, 249:918.PubMedCrossRefGoogle Scholar
  11. Sedlacek, H. H., Schulz, G., Steinstraesser, A., Kuhlmann, L., Schwarz, A., Seidel, L., Seemann, G., Kraemer, H. P., and Bosslet, K., 1988, “Monoclonal antibodies in tumor therapy — Present stage, chances and limitations,” Karger, Basel.Google Scholar
  12. Sehon, A. H., 1982, Suppression of IgE antibody responses with tolerogenic conjugates of allergens and haptens, in: “Regulation of the IgE antibody response,” Prog. Allergy. 32:161, K. Ishizaka, ed., Karger, Basel.CrossRefGoogle Scholar
  13. Sehon, A., 1989, Modulation of antibody responses by conjugates of antigens with monomethoxypolyethylene glycol, in: “Immunobiology of proteins and peptides V”, M. Z. Atassi, ed., Plenum Publishing Corporation, New York.Google Scholar
  14. Takata, M., Maiti, P. K., Kubo, R. T., Chen, Y., Holford-Strevens, V., Rector, E., and Sehon, A. H., 1990, Cloned suppressor T cells derived from mice tolerized with conjugates of antigen and monomethoxypolyethylene glycol, J. Immunol., 145:2846.PubMedGoogle Scholar
  15. Vogel, C-W., 1987, &#0x201C;Immunoconjugates: Antibody Conjugates in Radioimaging and Therapy of Cancer”, Oxford University Press, Oxford.Google Scholar
  16. Wilkinson, I., Jackson, C-J. C., Lang, G. M., Holford-Strevens, V., and Sehon, A. H., 1987, Tolerance induction in mice by conjugates of monoclonal immunoglobulins and monomethoxypolyethylene glycol. Transfer of tolerance by T cells and by T cell extracts, J. Immunol., 139:326.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Alec H. Sehon
    • 1
  1. 1.MRC Group for Allergy Research Department of ImmunologyThe University of ManitobaWinnipegCanada

Personalised recommendations