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. 1991 Jan 1;173(1):37–48. doi: 10.1084/jem.173.1.37

Effect of antigen/antibody ratio on macrophage uptake, processing, and presentation to T cells of antigen complexed with polyclonal antibodies

PMCID: PMC2118742  PMID: 1985125

Abstract

Activation of a galactosidase-specific murine T hybridoma clone and of a human tetanus toxoid-specific T clone by antigen-presenting cells (APC) was used to evaluate the regulatory function of antibodies complexed with the relevant antigen. Complexed antigen, in fact, is taken up with high efficiency thanks to Fc receptors borne by APC. Antibody/antigen ratio in the complexes proved to be a critical parameter in enhancing antigen presentation. Complexes in moderate antibody excess provided optimal T cell activation independently of the physical state of the complexes (precipitated by a second antibody or solubilized by complement). Complexes in extreme antibody excess, on the contrary, did not yield T cell activation although taken up by APC efficiently. The effect of antibodies at extreme excess was observed with substimulatory dose of antigen (loss of potentiation) and with optimal dose of antigen (loss of stimulation). An excess of specific polyclonal antibodies hampers proteolytic degradation of antigen in vitro, supporting the view that a similar mechanism may operate within the APC that have internalized immune complexes in extreme antibody excess. The possibility that immune complex forming in extreme antibody excess may turn off the T cell response is proposed as a regulatory mechanism.

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Selected References

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  1. Accolla R. S., Cina R., Montesoro E., Celada F. Antibody-mediated activation of genetically defective Escherichia coli beta-galactosidases by monoclonal antibodies produced by somatic cell hybrids. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2478–2482. doi: 10.1073/pnas.78.4.2478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BENACERRAF B., SEBESTYEN M., COOPER N. S. The clearance of antigen antibody complexes from the blood by the reticuloendothelial system. J Immunol. 1959 Feb;82(2):131–137. [PubMed] [Google Scholar]
  3. Benjamin D. C., Berzofsky J. A., East I. J., Gurd F. R., Hannum C., Leach S. J., Margoliash E., Michael J. G., Miller A., Prager E. M. The antigenic structure of proteins: a reappraisal. Annu Rev Immunol. 1984;2:67–101. doi: 10.1146/annurev.iy.02.040184.000435. [DOI] [PubMed] [Google Scholar]
  4. Celis E., Chang T. W. Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen. Science. 1984 Apr 20;224(4646):297–299. doi: 10.1126/science.6231724. [DOI] [PubMed] [Google Scholar]
  5. Chain B. M., Kay P. M., Feldmann M. The cellular pathway of antigen presentation: biochemical and functional analysis of antigen processing in dendritic cells and macrophages. Immunology. 1986 Jun;58(2):271–276. [PMC free article] [PubMed] [Google Scholar]
  6. Corradin G., Juillerat M. A., Engers H. D. Differential effects of two anti-apo-cytochrome c-specific monoclonal antibodies on the function of apo-cytochrome c-specific murine T cell clones. J Immunol. 1984 Dec;133(6):2915–2919. [PubMed] [Google Scholar]
  7. Daha M. R., van Es L. A. Fc- and complement receptor-dependent degradation of soluble immune complexes and stable immunoglobulin aggregates by guinea pig monocytes, peritoneal macrophages, and Kupffer cells. J Leukoc Biol. 1984 Nov;36(5):569–579. doi: 10.1002/jlb.36.5.569. [DOI] [PubMed] [Google Scholar]
  8. Deregt D., Parker M. D., Cox G. C., Babiuk L. A. Mapping of neutralizing epitopes to fragments of the bovine coronavirus E2 protein by proteolysis of antigen-antibody complexes. J Gen Virol. 1989 Mar;70(Pt 3):647–658. doi: 10.1099/0022-1317-70-3-647. [DOI] [PubMed] [Google Scholar]
  9. Ehlenberger A. G., Nussenzweig V. The role of membrane receptors for C3b and C3d in phagocytosis. J Exp Med. 1977 Feb 1;145(2):357–371. doi: 10.1084/jem.145.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eisenberg R. J., Long D., Pereira L., Hampar B., Zweig M., Cohen G. H. Effect of monoclonal antibodies on limited proteolysis of native glycoprotein gD of herpes simplex virus type 1. J Virol. 1982 Feb;41(2):478–488. doi: 10.1128/jvi.41.2.478-488.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guagliardi L. E., Koppelman B., Blum J. S., Marks M. S., Cresswell P., Brodsky F. M. Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment. Nature. 1990 Jan 11;343(6254):133–139. doi: 10.1038/343133a0. [DOI] [PubMed] [Google Scholar]
  12. Jemmerson R., Paterson Y. Mapping epitopes on a protein antigen by the proteolysis of antigen-antibody complexes. Science. 1986 May 23;232(4753):1001–1004. doi: 10.1126/science.2422757. [DOI] [PubMed] [Google Scholar]
  13. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  14. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kijlstra A., Van Es L. A., Daha M. R. Enhanced degradation of soluble immunoglobulin aggregates by macrophages in the presence of complement. Immunology. 1979 Jul;37(3):673–680. [PMC free article] [PubMed] [Google Scholar]
  16. Kimoto M., Fathman C. G. Antigen-reactive T cell clones. I. Transcomplementing hybrid I-A-region gene products function effectively in antigen presentation. J Exp Med. 1980 Oct 1;152(4):759–770. doi: 10.1084/jem.152.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
  18. Lanzavecchia A. Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. Annu Rev Immunol. 1990;8:773–793. doi: 10.1146/annurev.iy.08.040190.004013. [DOI] [PubMed] [Google Scholar]
  19. MOLLER G., WIGZELL H. ANTIBODY SYNTHESIS AT THE CELLULAR LEVEL. ANTIBODY-INDUCED SUPPRESSION OF 19S AND 7S ANTIBODY RESPONSE. J Exp Med. 1965 Jun 1;121:969–989. doi: 10.1084/jem.121.6.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Malynn B. A., Romeo D. T., Wortis H. H. Antigen-specific B cells efficiently present low doses of antigen for induction of T cell proliferation. J Immunol. 1985 Aug;135(2):980–988. [PubMed] [Google Scholar]
  21. Manca F., Clarke J. A., Miller A., Sercarz E. E., Shastri N. A limited region within hen egg-white lysozyme serves as the focus for a diversity of T cell clones. J Immunol. 1984 Oct;133(4):2075–2078. [PubMed] [Google Scholar]
  22. Manca F., Fenoglio D., Kunkl A., Cambiaggi C., Li Pira G., Celada F. B cells on the podium: regulatory roles of surface and secreted immunoglobulins. Immunol Today. 1988 Oct;9(10):300–303. doi: 10.1016/0167-5699(88)91321-7. [DOI] [PubMed] [Google Scholar]
  23. Manca F., Fenoglio D., Kunkl A., Cambiaggi C., Sasso M., Celada F. Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies. A possible influence of paratope specificity on the mode of antigen processing. J Immunol. 1988 May 1;140(9):2893–2898. [PubMed] [Google Scholar]
  24. Manca F., Migliorini P., Bombardieri S., Celada F. An enzymatically active antigen-antibody probe to measure circulating immune complexes by competition. I. Use of Escherichia coli beta-galactosidase in the probe and of bovine conglutinin as the complex-binding reagent. Clin Immunol Immunopathol. 1980 Jun;16(2):131–141. doi: 10.1016/0090-1229(80)90197-x. [DOI] [PubMed] [Google Scholar]
  25. McCoy K. L., Schwartz R. H. The role of intracellular acidification in antigen processing. Immunol Rev. 1988 Dec;106:129–147. doi: 10.1111/j.1600-065x.1988.tb00777.x. [DOI] [PubMed] [Google Scholar]
  26. Mellman I., Koch T., Healey G., Hunziker W., Lewis V., Plutner H., Miettinen H., Vaux D., Moore K., Stuart S. Structure and function of Fc receptors on macrophages and lymphocytes. J Cell Sci Suppl. 1988;9:45–65. doi: 10.1242/jcs.1988.supplement_9.3. [DOI] [PubMed] [Google Scholar]
  27. Miller G. W., Nussenzweig V. A new complement function: solubilization of antigen-antibody aggregates. Proc Natl Acad Sci U S A. 1975 Feb;72(2):418–422. doi: 10.1073/pnas.72.2.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ozaki S., Berzofsky J. A. Antibody conjugates mimic specific B cell presentation of antigen: relationship between T and B cell specificity. J Immunol. 1987 Jun 15;138(12):4133–4142. [PubMed] [Google Scholar]
  29. Sheshberadaran H., Payne L. G. Protein antigen-monoclonal antibody contact sites investigated by limited proteolysis of monoclonal antibody-bound antigen: protein "footprinting". Proc Natl Acad Sci U S A. 1988 Jan;85(1):1–5. doi: 10.1073/pnas.85.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Unkeless J. C., Scigliano E., Freedman V. H. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988;6:251–281. doi: 10.1146/annurev.iy.06.040188.001343. [DOI] [PubMed] [Google Scholar]
  32. Unkeless J. C. The presence of two Fc receptors on mouse macrophages: evidence from a variant cell line and differential trypsin sensitivity. J Exp Med. 1977 Apr 1;145(4):931–945. doi: 10.1084/jem.145.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Watts C., Davidson H. W. Endocytosis and recycling of specific antigen by human B cell lines. EMBO J. 1988 Jul;7(7):1937–1945. doi: 10.1002/j.1460-2075.1988.tb03031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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