Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Jan 1;171(1):211–219. doi: 10.1084/jem.171.1.211

In vivo effects of monoclonal antibodies to distinct epitopes of Qa-2 antigens

PMCID: PMC2187671  PMID: 1688608

Abstract

The effects of in vivo treatment with anti-Qa-2 mAbs on in vivo and in vitro parameters of T cell immunity have been examined. Two anti-Qa-2 mAbs of the same isotype and with similar avidities but directed against distinct epitopes of the same Qa-2 molecules were studied. mAb 1-1-2 was found to induce rapid T cell depletion, with maximal effect observed within 2-3 d, while administration of mAb 1-9-9 caused little or no depletion in the first few days, and reached maximal effect only by day 8. Surprisingly, administration of both antibodies resulted in a depletion pattern similar to that of the nondepleting antibody 1-9-9. Consistent with these effects on T cell depletion, treatment with 1-1-2 caused significant prolongation of survival of allogeneic skin grafts placed 1 d after antibody administration, while treatment with 1-9-9 or with the combination of both antibodies caused no prolongation. In an attempt to determine the mechanism of this phenomenon, we examined Qa-2 expression on the cell surface by flow microfluorometry after treatment with each of the two mAbs. Our data indicate that mAb 1-9-9 mediates significantly greater modulation of Qa-2 expression from the surface of peripheral T cells within 1 d than does mAb 1-1-2. Apparently, therefore, modulation occurs more rapidly than cell clearance, and the efficiency of T cell depletion and consequent immune suppression is correlated inversely with the ability of each mAb to cause modulation. The ability of 1-9-9 to cause Qa-2 modulation suggests that it may react with a determinant on this molecule of physiological relevance to the natural ligand interactions of Qa-2 antigens.

Full Text

The Full Text of this article is available as a PDF (589.1 KB).

Selected References

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

  1. Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. doi: 10.1038/312548a0. [DOI] [PubMed] [Google Scholar]
  2. Cosimi A. B., Burton R. C., Colvin R. B., Goldstein G., Delmonico F. L., LaQuaglia M. P., Tolkoff-Rubin N., Rubin R. H., Herrin J. T., Russell P. S. Treatment of acute renal allograft rejection with OKT3 monoclonal antibody. Transplantation. 1981 Dec;32(6):535–539. doi: 10.1097/00007890-198112000-00018. [DOI] [PubMed] [Google Scholar]
  3. Ghobrial R. R., Boublik M., Winn H. J., Auchincloss H., Jr In vivo use of monoclonal antibodies against murine T cell antigens. Clin Immunol Immunopathol. 1989 Sep;52(3):486–506. doi: 10.1016/0090-1229(89)90162-1. [DOI] [PubMed] [Google Scholar]
  4. Goding J. W. Use of staphylococcal protein A as an immunological reagent. J Immunol Methods. 1978;20:241–253. doi: 10.1016/0022-1759(78)90259-4. [DOI] [PubMed] [Google Scholar]
  5. Gunter K. C., Malek T. R., Shevach E. M. T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4. J Exp Med. 1984 Mar 1;159(3):716–730. doi: 10.1084/jem.159.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hale G., Clark M., Waldmann H. Therapeutic potential of rat monoclonal antibodies: isotype specificity of antibody-dependent cell-mediated cytotoxicity with human lymphocytes. J Immunol. 1985 May;134(5):3056–3061. [PubMed] [Google Scholar]
  7. Janeway C. A., Jr, Conrad P. J., Lerner E. A., Babich J., Wettstein P., Murphy D. B. Monoclonal antibodies specific for Ia glycoproteins raised by immunization with activated T cells: possible role of T cellbound Ia antigens as targets of immunoregulatory T cells. J Immunol. 1984 Feb;132(2):662–667. [PubMed] [Google Scholar]
  8. Kawamura H., Sharrow S. O., Alling D. W., Stephany D., York-Jolley J., Berzofsky J. A. Interleukin 2 receptor expression in unstimulated murine splenic T cells. Localization to L3T4+ cells and regulation by non-H-2-linked genes. J Exp Med. 1986 Jun 1;163(6):1376–1390. doi: 10.1084/jem.163.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kelley V. E., Gaulton G. N., Strom T. B. Inhibitory effects of anti-interleukin 2 receptor and anti-L3T4 antibodies on delayed type hypersensitivity: the role of complement and epitope. J Immunol. 1987 May 1;138(9):2771–2775. [PubMed] [Google Scholar]
  10. Kirkman R. L., Araujo J. L., Busch G. J., Carpenter C. B., Milford E. L., Reinherz E. L., Schlossman S. F., Strom T. B., Tilney N. L. Treatment of acute renal allograft rejection with monoclonal anti-T12 antibody. Transplantation. 1983 Dec;36(6):620–626. doi: 10.1097/00007890-198336060-00005. [DOI] [PubMed] [Google Scholar]
  11. Kummer U., Thierfelder S., Hoffmann-Fezer G., Schuh R. In vivo immunosuppression by pan-T cell antibodies relates to their isotype and to their C1q uptake. J Immunol. 1987 Jun 15;138(12):4069–4074. [PubMed] [Google Scholar]
  12. Malek T. R., Ortega G., Chan C., Kroczek R. A., Shevach E. M. Role of Ly-6 in lymphocyte activation. II. Induction of T cell activation by monoclonal anti-Ly-6 antibodies. J Exp Med. 1986 Sep 1;164(3):709–722. doi: 10.1084/jem.164.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Meuer S. C., Hodgdon J. C., Hussey R. E., Protentis J. P., Schlossman S. F., Reinherz E. L. Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J Exp Med. 1983 Sep 1;158(3):988–993. doi: 10.1084/jem.158.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller M. H., Powell J. I., Sharrow S. O., Schultz A. R. Rapid data collection, analysis, and graphics for flow microfluorometry instrumentation. Rev Sci Instrum. 1978 Aug;49(8):1137–1142. doi: 10.1063/1.1135535. [DOI] [PubMed] [Google Scholar]
  15. Rabinowitz R., Sharrow S. O., Chatterjee-Das S., Rogers M. J., Sachs D. H. Qa alloantigen expression on functional T lymphocytes from spleen and thymus. Immunogenetics. 1986;24(6):391–401. doi: 10.1007/BF00377958. [DOI] [PubMed] [Google Scholar]
  16. Segal D. M., Titus J. A., Stephany D. A. Fluorescence flow cytometry in the study of lymphoid cell receptors. Methods Enzymol. 1987;150:478–492. doi: 10.1016/0076-6879(87)50101-x. [DOI] [PubMed] [Google Scholar]
  17. Sharrow S. O., Arn J. S., Stroynowski I., Hood L., Sachs D. H. Epitope clusters of Qa-2 antigens defined by a panel of new monoclonal antibodies. J Immunol. 1989 May 15;142(10):3495–3502. [PubMed] [Google Scholar]
  18. Soloski M. J., Vernachio J., Einhorn G., Lattimore A. Qa gene expression: biosynthesis and secretion of Qa-2 molecules in activated T cells. Proc Natl Acad Sci U S A. 1986 May;83(9):2949–2953. doi: 10.1073/pnas.83.9.2949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stiernberg J., Low M. G., Flaherty L., Kincade P. W. Removal of lymphocyte surface molecules with phosphatidylinositol-specific phospholipase C: effects on mitogen responses and evidence that ThB and certain Qa antigens are membrane-anchored via phosphatidylinositol. J Immunol. 1987 Jun 1;138(11):3877–3884. [PubMed] [Google Scholar]
  20. Stohl W., Posnett D. N., Chiorazzi N. Differential immunomodulation by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell activation: dependence upon the individual anti-CD3 monoclonal antibody used for activation. Cell Immunol. 1988 Oct 1;116(1):73–85. doi: 10.1016/0008-8749(88)90211-0. [DOI] [PubMed] [Google Scholar]
  21. Takada S., Engleman E. G. Evidence for an association between CD8 molecules and the T cell receptor complex on cytotoxic T cells. J Immunol. 1987 Nov 15;139(10):3231–3235. [PubMed] [Google Scholar]
  22. Thistlethwaite J. R., Jr, Cosimi A. B., Delmonico F. L., Rubin R. H., Talkoff-Rubin N., Nelson P. W., Fang L., Russell P. S. Evolving use of OKT3 monoclonal antibody for treatment of renal allograft rejection. Transplantation. 1984 Dec;38(6):695–701. doi: 10.1097/00007890-198412000-00029. [DOI] [PubMed] [Google Scholar]
  23. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yeh E. T., Reiser H., Benacerraf B., Rock K. L. The expression, function, and ontogeny of a novel T cell-activating protein, TAP, in the thymus. J Immunol. 1986 Aug 15;137(4):1232–1238. [PubMed] [Google Scholar]

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

RESOURCES