Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Dec 1;172(6):1665–1672. doi: 10.1084/jem.172.6.1665

Expression cloning of a human Fc receptor for IgA

PMCID: PMC2188749  PMID: 2258698

Abstract

IgA, the predominant isotype in secretions, mediates the neutralization and removal of environmental antigens from mucosal sites. Although cell surface receptors for the Fc region of IgA (Fc alpha R) have been implicated in a variety of immune effector mechanisms, the molecular features of Fc alpha R remain only marginally characterized. In this report, we describe the isolation of a clone from a myeloid cell line cDNA library that directs the expression of a cell surface molecule with IgA binding specificity. The cDNA encodes a peptide of Mr 30,000 including a putative transmembrane region with features atypical of conventional membrane-anchored proteins. Databank searches indicate that the human myeloid cell Fc alpha R sequence is unique, is a member of the immunoglobulin gene superfamily, and is related to Fc receptors for IgG (Fc gamma RI, II, and III) and IgE (Fc epsilon RI).

Full Text

The Full Text of this article is available as a PDF (1,001.0 KB).

Selected References

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

  1. Albrechtsen M., Yeaman G. R., Kerr M. A. Characterization of the IgA receptor from human polymorphonuclear leucocytes. Immunology. 1988 Jun;64(2):201–205. [PMC free article] [PubMed] [Google Scholar]
  2. Blank U., Ra C., Miller L., White K., Metzger H., Kinet J. P. Complete structure and expression in transfected cells of high affinity IgE receptor. Nature. 1989 Jan 12;337(6203):187–189. doi: 10.1038/337187a0. [DOI] [PubMed] [Google Scholar]
  3. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chevailler A., Monteiro R. C., Kubagawa H., Cooper M. D. Immunofluorescence analysis of IgA binding by human mononuclear cells in blood and lymphoid tissue. J Immunol. 1989 Apr 1;142(7):2244–2249. [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  7. Cosman D., Cerretti D. P., Larsen A., Park L., March C., Dower S., Gillis S., Urdal D. Cloning, sequence and expression of human interleukin-2 receptor. Nature. 1984 Dec 20;312(5996):768–771. doi: 10.1038/312768a0. [DOI] [PubMed] [Google Scholar]
  8. Dayhoff M. O., Barker W. C., Hunt L. T. Establishing homologies in protein sequences. Methods Enzymol. 1983;91:524–545. doi: 10.1016/s0076-6879(83)91049-2. [DOI] [PubMed] [Google Scholar]
  9. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fanger M. W., Goldstine S. N., Shen L. Cytofluorographic analysis of receptors for IgA on human polymorphonuclear cells and monocytes and the correlation of receptor expression with phagocytosis. Mol Immunol. 1983 Sep;20(9):1019–1027. doi: 10.1016/0161-5890(83)90043-3. [DOI] [PubMed] [Google Scholar]
  11. Fanger M. W., Lydyard P. M. Receptors for IgA on human lymphocytes--I. detection and specificity. Mol Immunol. 1981 Mar;18(3):189–195. doi: 10.1016/0161-5890(81)90085-7. [DOI] [PubMed] [Google Scholar]
  12. Fanger M. W., Shen L., Pugh J., Bernier G. M. Subpopulations of human peripheral granulocyes and monocytes express receptors for IgA. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3640–3644. doi: 10.1073/pnas.77.6.3640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ferguson M. A., Williams A. F. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem. 1988;57:285–320. doi: 10.1146/annurev.bi.57.070188.001441. [DOI] [PubMed] [Google Scholar]
  14. Ferreri N. R., Howland W. C., Spiegelberg H. L. Release of leukotrienes C4 and B4 and prostaglandin E2 from human monocytes stimulated with aggregated IgG, IgA, and IgE. J Immunol. 1986 Jun 1;136(11):4188–4193. [PubMed] [Google Scholar]
  15. Gauldie J., Richards C., Lamontagne L. Fc receptors for IgA and other immunoglobulins on resident and activated alveolar macrophages. Mol Immunol. 1983 Sep;20(9):1029–1037. doi: 10.1016/0161-5890(83)90044-5. [DOI] [PubMed] [Google Scholar]
  16. Gorter A., Hiemstra P. S., Leijh P. C., van der Sluys M. E., van den Barselaar M. T., van Es L. A., Daha M. R. IgA- and secretory IgA-opsonized S. aureus induce a respiratory burst and phagocytosis by polymorphonuclear leucocytes. Immunology. 1987 Jul;61(3):303–309. [PMC free article] [PubMed] [Google Scholar]
  17. Grundy H. O., Peltz G., Moore K. W., Golbus M. S., Jackson L. G., Lebo R. V. The polymorphic Fc gamma receptor II gene maps to human chromosome 1q. Immunogenetics. 1989;29(5):331–339. doi: 10.1007/BF00352843. [DOI] [PubMed] [Google Scholar]
  18. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  19. Gupta S., Platsoucas C. D., Good R. A. Receptors for IgA on a subpopulation of human B lymphocytes. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4025–4028. doi: 10.1073/pnas.76.8.4025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  21. Hibbs M. L., Selvaraj P., Carpén O., Springer T. A., Kuster H., Jouvin M. H., Kinet J. P. Mechanisms for regulating expression of membrane isoforms of Fc gamma RIII (CD16). Science. 1989 Dec 22;246(4937):1608–1611. doi: 10.1126/science.2531918. [DOI] [PubMed] [Google Scholar]
  22. Huppi K., Mock B. A., Hilgers J., Kochan J., Kinet J. P. Receptors for Fc epsilon and Fc gamma are linked on mouse chromosome 1. J Immunol. 1988 Oct 15;141(8):2807–2810. [PubMed] [Google Scholar]
  23. Karpovsky B., Titus J. A., Stephany D. A., Segal D. M. Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies. J Exp Med. 1984 Dec 1;160(6):1686–1701. doi: 10.1084/jem.160.6.1686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kroczek R. A., Siebert E. Optimization of northern analysis by vacuum-blotting, RNA-transfer visualization, and ultraviolet fixation. Anal Biochem. 1990 Jan;184(1):90–95. doi: 10.1016/0003-2697(90)90017-4. [DOI] [PubMed] [Google Scholar]
  25. Kurosaki T., Ravetch J. V. A single amino acid in the glycosyl phosphatidylinositol attachment domain determines the membrane topology of Fc gamma RIII. Nature. 1989 Dec 14;342(6251):805–807. doi: 10.1038/342805a0. [DOI] [PubMed] [Google Scholar]
  26. Lanier L. L., Cwirla S., Yu G., Testi R., Phillips J. H. Membrane anchoring of a human IgG Fc receptor (CD16) determined by a single amino acid. Science. 1989 Dec 22;246(4937):1611–1613. doi: 10.1126/science.2531919. [DOI] [PubMed] [Google Scholar]
  27. Maliszewski C. R., Shen L., Fanger M. W. The expression of receptors for IgA on human monocytes and calcitriol-treated HL-60 cells. J Immunol. 1985 Dec;135(6):3878–3881. [PubMed] [Google Scholar]
  28. Monteiro R. C., Kubagawa H., Cooper M. D. Cellular distribution, regulation, and biochemical nature of an Fc alpha receptor in humans. J Exp Med. 1990 Mar 1;171(3):597–613. doi: 10.1084/jem.171.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mosley B., Beckmann M. P., March C. J., Idzerda R. L., Gimpel S. D., VandenBos T., Friend D., Alpert A., Anderson D., Jackson J. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. doi: 10.1016/0092-8674(89)90295-x. [DOI] [PubMed] [Google Scholar]
  30. Ravetch J. V., Perussia B. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med. 1989 Aug 1;170(2):481–497. doi: 10.1084/jem.170.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Saxon A., Feldhaus J., Robins R. A. Single step separation of human T and B cells using AET treated srbc rosettes. J Immunol Methods. 1976;12(3-4):285–288. doi: 10.1016/0022-1759(76)90050-8. [DOI] [PubMed] [Google Scholar]
  32. Schmid C. W., Jelinek W. R. The Alu family of dispersed repetitive sequences. Science. 1982 Jun 4;216(4550):1065–1070. doi: 10.1126/science.6281889. [DOI] [PubMed] [Google Scholar]
  33. Seed B., Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987 May;84(10):3365–3369. doi: 10.1073/pnas.84.10.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shen L., Fanger M. W. Secretory IgA antibodies synergize with IgG in promoting ADCC by human polymorphonuclear cells, monocytes, and lymphocytes. Cell Immunol. 1981 Mar 15;59(1):75–81. doi: 10.1016/0008-8749(81)90435-4. [DOI] [PubMed] [Google Scholar]
  35. Shen L., Lasser R., Fanger M. W. My 43, a monoclonal antibody that reacts with human myeloid cells inhibits monocyte IgA binding and triggers function. J Immunol. 1989 Dec 15;143(12):4117–4122. [PubMed] [Google Scholar]
  36. Shen L., Maliszewski C. R., Rigby W. F., Fanger M. W. IgA-mediated effector function of HL-60 cells following treatment with calcitriol. Mol Immunol. 1986 Jun;23(6):611–618. doi: 10.1016/0161-5890(86)90097-0. [DOI] [PubMed] [Google Scholar]
  37. Simmons D., Seed B. The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature. 1988 Jun 9;333(6173):568–570. doi: 10.1038/333568a0. [DOI] [PubMed] [Google Scholar]
  38. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  39. Underdown B. J., Schiff J. M. Immunoglobulin A: strategic defense initiative at the mucosal surface. Annu Rev Immunol. 1986;4:389–417. doi: 10.1146/annurev.iy.04.040186.002133. [DOI] [PubMed] [Google Scholar]
  40. Waneck G. L., Stein M. E., Flavell R. A. Conversion of a PI-anchored protein to an integral membrane protein by a single amino acid mutation. Science. 1988 Aug 5;241(4866):697–699. doi: 10.1126/science.3399901. [DOI] [PubMed] [Google Scholar]
  41. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  42. Yeaman G. R., Kerr M. A. Opsonization of yeast by human serum IgA anti-mannan antibodies and phagocytosis by human polymorphonuclear leucocytes. Clin Exp Immunol. 1987 Apr;68(1):200–208. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES