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. 1989 Sep;86(18):7118–7122. doi: 10.1073/pnas.86.18.7118

Binding site for IgE of the human lymphocyte low-affinity Fc epsilon receptor (Fc epsilon RII/CD23) is confined to the domain homologous with animal lectins.

B Bettler 1, R Maier 1, D Rüegg 1, H Hofstetter 1
PMCID: PMC298006  PMID: 2476812

Abstract

The lymphocyte low-affinity receptor for IgE (Fc epsilon RII) is involved in two seemingly unrelated processes: (i) promotion of general B-cell growth and (ii) isotype-specific IgE synthesis. To characterize domains of Fc epsilon RII important for effector function, we have expressed Fc epsilon RII mutants in mammalian cells. The results show that the IgE-binding region of Fc epsilon RII corresponds almost exactly to a domain of 123 amino acid residues homologous with the carbohydrate-binding domain of C-type animal lectins. With the recent demonstration that Fc epsilon RII binds to IgE independently of any lectin-like activity [Vercelli, D., Helm, B., Marsh, P., Padlan, E., Geha, R.S. & Gould, H. (1989) Nature (London) 338, 649-651], it is now clear that, in this case, the lectin module has evolved to interact with a protein rather than a carbohydrate moiety. The epitopes of several independent monoclonal antibodies that inhibit the binding of IgE to Fc epsilon RII are clustered within the lectin-like domain. Some of these antibodies are also known to suppress, isotype-specifically, the interleukin 4-promoted IgE synthesis from peripheral blood mononuclear cells or the spontaneous synthesis of IgE by B cells isolated from atopic donors. The epitope of MHM6, an anti-F epsilon RII monoclonal antibody delivering an epitope-restricted growth-promoting effect on B cells, is also located within the lectin-like domain. Thus, the lectin module of Fc epsilon RII not only acts as a carbohydrate-independent, isotype-specific Fc receptor but may also participate in the general regulation of B-cell growth.

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Selected References

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

  1. Asselbergs F. A., Will H., Wingfield P., Hirschi M. A recombinant Chinese hamster ovary cell line containing a 300-fold amplified tetramer of the hepatitis B genome together with a double selection marker expresses high levels of viral protein. J Mol Biol. 1986 Jun 5;189(3):401–411. doi: 10.1016/0022-2836(86)90312-8. [DOI] [PubMed] [Google Scholar]
  2. Bonnefoy J. Y., Aubry J. P., Peronne C., Wijdenes J., Banchereau J. Production and characterization of a monoclonal antibody specific for the human lymphocyte low affinity receptor for IgE: CD 23 is a low affinity receptor for IgE. J Immunol. 1987 May 1;138(9):2970–2978. [PubMed] [Google Scholar]
  3. Brownstone A., Mitchison N. A., Pitt-Rivers R. Chemical and serological studies with an iodine-containing synthetic immunological determinant 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) and related compounds. Immunology. 1966 May;10(5):465–479. [PMC free article] [PubMed] [Google Scholar]
  4. Capron A., Dessaint J. P., Capron M., Ouma J. H., Butterworth A. E. Immunity to schistosomes: progress toward vaccine. Science. 1987 Nov 20;238(4830):1065–1072. doi: 10.1126/science.3317823. [DOI] [PubMed] [Google Scholar]
  5. Carini C., Margolick J., Yodoi J., Ishizaka K. Formation of IgE-binding factors by T cells of patients infected with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9214–9218. doi: 10.1073/pnas.85.23.9214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Delespesse G., Sarfati M., Hofstetter H. Human IgE-binding factors. Immunol Today. 1989 May;10(5):159–164. doi: 10.1016/0167-5699(89)90173-4. [DOI] [PubMed] [Google Scholar]
  7. Dorsch-Häsler K., Keil G. M., Weber F., Jasin M., Schaffner W., Koszinowski U. H. A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8325–8329. doi: 10.1073/pnas.82.24.8325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drickamer K. Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem. 1988 Jul 15;263(20):9557–9560. [PubMed] [Google Scholar]
  9. Gordon J., Flores-Romo L., Cairns J. A., Millsum M. J., Lane P. J., Johnson G. D., MacLennan I. C. CD23: a multi-functional receptor/lymphokine? Immunol Today. 1989 May;10(5):153–157. doi: 10.1016/0167-5699(89)90171-0. [DOI] [PubMed] [Google Scholar]
  10. Gordon J., Webb A. J., Guy G. R., Walker L. Triggering of B lymphocytes through CD23: epitope mapping and studies using antibody derivatives indicate an allosteric mechanism of signalling. Immunology. 1987 Apr;60(4):517–521. [PMC free article] [PubMed] [Google Scholar]
  11. Gordon J., Webb A. J., Walker L., Guy G. R., Rowe M. Evidence for an association between CD23 and the receptor for a low molecular weight B cell growth factor. Eur J Immunol. 1986 Dec;16(12):1627–1630. doi: 10.1002/eji.1830161225. [DOI] [PubMed] [Google Scholar]
  12. Haynes J., Weissmann C. Constitutive, long-term production of human interferons by hamster cells containing multiple copies of a cloned interferon gene. Nucleic Acids Res. 1983 Feb 11;11(3):687–706. doi: 10.1093/nar/11.3.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hogg N. The structure and function of Fc receptors. Immunol Today. 1988 Jul-Aug;9(7-8):185–187. doi: 10.1016/0167-5699(88)91206-6. [DOI] [PubMed] [Google Scholar]
  14. Ikuta K., Takami M., Kim C. W., Honjo T., Miyoshi T., Tagaya Y., Kawabe T., Yodoi J. Human lymphocyte Fc receptor for IgE: sequence homology of its cloned cDNA with animal lectins. Proc Natl Acad Sci U S A. 1987 Feb;84(3):819–823. doi: 10.1073/pnas.84.3.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ishizaka K. IgE-binding factors and regulation of the IgE antibody response. Annu Rev Immunol. 1988;6:513–534. doi: 10.1146/annurev.iy.06.040188.002501. [DOI] [PubMed] [Google Scholar]
  16. Ishizaka K., Ishizaka T. Identification of gamma-E-antibodies as a carrier of reaginic activity. J Immunol. 1967 Dec;99(6):1187–1198. [PubMed] [Google Scholar]
  17. Kikutani H., Inui S., Sato R., Barsumian E. L., Owaki H., Yamasaki K., Kaisho T., Uchibayashi N., Hardy R. R., Hirano T. Molecular structure of human lymphocyte receptor for immunoglobulin E. Cell. 1986 Dec 5;47(5):657–665. doi: 10.1016/0092-8674(86)90508-8. [DOI] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Lüdin C., Hofstetter H., Sarfati M., Levy C. A., Suter U., Alaimo D., Kilchherr E., Frost H., Delespesse G. Cloning and expression of the cDNA coding for a human lymphocyte IgE receptor. EMBO J. 1987 Jan;6(1):109–114. doi: 10.1002/j.1460-2075.1987.tb04726.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Metzger H., Kinet J. P. How antibodies work: focus on Fc receptors. FASEB J. 1988 Jan;2(1):3–11. doi: 10.1096/fasebj.2.1.3275562. [DOI] [PubMed] [Google Scholar]
  21. Patthy L. Detecting distant homologies of mosaic proteins. Analysis of the sequences of thrombomodulin, thrombospondin complement components C9, C8 alpha and C8 beta, vitronectin and plasma cell membrane glycoprotein PC-1. J Mol Biol. 1988 Aug 20;202(4):689–696. doi: 10.1016/0022-2836(88)90550-5. [DOI] [PubMed] [Google Scholar]
  22. Pène J., Rousset F., Brière F., Chrétien I., Bonnefoy J. Y., Spits H., Yokota T., Arai N., Arai K., Banchereau J. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6880–6884. doi: 10.1073/pnas.85.18.6880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rector E., Nakajima T., Rocha C., Duncan D., Lestourgeon D., Mitchell R. S., Fischer J., Sehon A. H., Delespesse G. Detection and characterization of monoclonal antibodies specific to IgE receptors on human lymphocytes by flow cytometry. Immunology. 1985 Jul;55(3):481–488. [PMC free article] [PubMed] [Google Scholar]
  24. Rowe M., Hildreth J. E., Rickinson A. B., Epstein M. A. Monoclonal antibodies to Epstein-Barr virus-induced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T-cell cytotoxicity. Int J Cancer. 1982 Apr 15;29(4):373–381. doi: 10.1002/ijc.2910290403. [DOI] [PubMed] [Google Scholar]
  25. Sarfati M., Bron D., Lagneaux L., Fonteyn C., Frost H., Delespesse G. Elevation of IgE-binding factors in serum of patients with B cell-derived chronic lymphocytic leukemia. Blood. 1988 Jan;71(1):94–98. [PubMed] [Google Scholar]
  26. Sarfati M., Delespesse G. Possible role of human lymphocyte receptor for IgE (CD23) or its soluble fragments in the in vitro synthesis of human IgE. J Immunol. 1988 Oct 1;141(7):2195–2199. [PubMed] [Google Scholar]
  27. Sharon N., Lis H. Lectins: cell-agglutinating and sugar-specific proteins. Science. 1972 Sep 15;177(4053):949–959. doi: 10.1126/science.177.4053.949. [DOI] [PubMed] [Google Scholar]
  28. Stoolman L. M. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
  29. Suemura M., Kikutani H., Barsumian E. L., Hattori Y., Kishimoto S., Sato R., Maeda A., Nakamura H., Owaki H., Hardy R. R. Monoclonal anti-Fc epsilon receptor antibodies with different specificities and studies on the expression of Fc epsilon receptors on human B and T cells. J Immunol. 1986 Aug 15;137(4):1214–1220. [PubMed] [Google Scholar]
  30. Suter U., Bastos R., Hofstetter H. Molecular structure of the gene and the 5'-flanking region of the human lymphocyte immunoglobulin E receptor. Nucleic Acids Res. 1987 Sep 25;15(18):7295–7308. doi: 10.1093/nar/15.18.7295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Urlaub G., Chasin L. A. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4216–4220. doi: 10.1073/pnas.77.7.4216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vercelli D., Helm B., Marsh P., Padlan E., Geha R. S., Gould H. The B-cell binding site on human immunoglobulin E. Nature. 1989 Apr 20;338(6217):649–651. doi: 10.1038/338649a0. [DOI] [PubMed] [Google Scholar]
  33. Wang F., Gregory C. D., Rowe M., Rickinson A. B., Wang D., Birkenbach M., Kikutani H., Kishimoto T., Kieff E. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23. Proc Natl Acad Sci U S A. 1987 May;84(10):3452–3456. doi: 10.1073/pnas.84.10.3452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Weber F., Schaffner W. Simian virus 40 enhancer increases RNA polymerase density within the linked gene. Nature. 1985 May 2;315(6014):75–77. doi: 10.1038/315075a0. [DOI] [PubMed] [Google Scholar]
  35. Yokota A., Kikutani H., Tanaka T., Sato R., Barsumian E. L., Suemura M., Kishimoto T. Two species of human Fc epsilon receptor II (Fc epsilon RII/CD23): tissue-specific and IL-4-specific regulation of gene expression. Cell. 1988 Nov 18;55(4):611–618. doi: 10.1016/0092-8674(88)90219-x. [DOI] [PubMed] [Google Scholar]
  36. Yukawa K., Kikutani H., Owaki H., Yamasaki K., Yokota A., Nakamura H., Barsumian E. L., Hardy R. R., Suemura M., Kishimoto T. A B cell-specific differentiation antigen, CD23, is a receptor for IgE (Fc epsilon R) on lymphocytes. J Immunol. 1987 Apr 15;138(8):2576–2580. [PubMed] [Google Scholar]

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