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. 1992 Dec;11(13):4861–4868. doi: 10.1002/j.1460-2075.1992.tb05592.x

Lineage-independent activation of immune system effector function by myeloid Fc receptors.

W Kolanus 1, C Romeo 1, B Seed 1
PMCID: PMC556962  PMID: 1464313

Abstract

An emerging theme in immunology finds receptors which initiate cellular effector programs forming multichain complexes in which the ligand recognition elements associate with one or more 'trigger molecules' whose aggregation initiates a signal transduction cascade. The sequence motifs constituting the active sites of these trigger molecules are found in the T cell and B cell antigen receptors, and some Fc receptors, and appear to be central to effector function activation. For example, of the many molecules that mimic or potentiate the action of the T cell antigen receptor (TCR), none have yet been found to initiate effector programs autonomously in cells lacking TCR. We have devised two strategies to study activation mediated by myeloid Fc receptors, which appear not to associate with trigger molecules: the use of primary human cytolytic T cells as surrogate effector cells for genetically delivered receptors, and the use of vaccinia virus vectors to introduce genetically modified receptors into primary human monocytes. Using these approaches, we have found that the cytoplasmic domains of two Fc receptors show comparable function to equivalent domains of the trigger molecule family, but are not homologous to members of that family.

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Selected References

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  1. Amigorena S., Bonnerot C., Drake J. R., Choquet D., Hunziker W., Guillet J. G., Webster P., Sautes C., Mellman I., Fridman W. H. Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes. Science. 1992 Jun 26;256(5065):1808–1812. doi: 10.1126/science.1535455. [DOI] [PubMed] [Google Scholar]
  2. Anderson P., Caligiuri M., O'Brien C., Manley T., Ritz J., Schlossman S. F. Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2274–2278. doi: 10.1073/pnas.87.6.2274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balk S., Terhorst C. Relationship between the T-cell receptor-T3 complex and Thy-1. Immunol Ser. 1989;45:411–416. [PubMed] [Google Scholar]
  4. 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]
  5. Bonnerot C., Amigorena S., Choquet D., Pavlovich R., Choukroun V., Fridman W. H. Role of associated gamma-chain in tyrosine kinase activation via murine Fc gamma RIII. EMBO J. 1992 Jul;11(7):2747–2757. doi: 10.1002/j.1460-2075.1992.tb05340.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boyle D. B., Coupar B. E. A dominant selectable marker for the construction of recombinant poxviruses. Gene. 1988 May 15;65(1):123–128. doi: 10.1016/0378-1119(88)90424-6. [DOI] [PubMed] [Google Scholar]
  7. Connor R. I., Shen L., Fanger M. W. Evaluation of the antibody-dependent cytotoxic capabilities of individual human monocytes. Role of Fc gamma RI and Fc gamma RII and the effects of cytokines at the single cell level. J Immunol. 1990 Sep 1;145(5):1483–1489. [PubMed] [Google Scholar]
  8. Engelhardt W., Gorczytza H., Butterweck A., Mönkemann H., Frey J. Structural requirements of the cytoplasmic domains of the human macrophage Fc gamma receptor IIa and B cell Fc gamma receptor IIb2 for the endocytosis of immune complexes. Eur J Immunol. 1991 Sep;21(9):2227–2238. doi: 10.1002/eji.1830210934. [DOI] [PubMed] [Google Scholar]
  9. Falkner F. G., Moss B. Escherichia coli gpt gene provides dominant selection for vaccinia virus open reading frame expression vectors. J Virol. 1988 Jun;62(6):1849–1854. doi: 10.1128/jvi.62.6.1849-1854.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fanger M. W., Shen L., Graziano R. F., Guyre P. M. Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today. 1989 Mar;10(3):92–99. doi: 10.1016/0167-5699(89)90234-X. [DOI] [PubMed] [Google Scholar]
  11. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gardner P. Calcium and T lymphocyte activation. Cell. 1989 Oct 6;59(1):15–20. doi: 10.1016/0092-8674(89)90865-9. [DOI] [PubMed] [Google Scholar]
  13. Graziano R. F., Fanger M. W. Fc gamma RI and Fc gamma RII on monocytes and granulocytes are cytotoxic trigger molecules for tumor cells. J Immunol. 1987 Nov 15;139(10):3536–3541. [PubMed] [Google Scholar]
  14. Graziano R. F., Fanger M. W. Human monocyte-mediated cytotoxicity: the use of Ig-bearing hybridomas as target cells to detect trigger molecules on the monocyte cell surface. J Immunol. 1987 Feb 1;138(3):945–950. [PubMed] [Google Scholar]
  15. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  16. 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]
  17. Huang M. M., Indik Z., Brass L. F., Hoxie J. A., Schreiber A. D., Brugge J. S. Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins including Fc gamma RII. J Biol Chem. 1992 Mar 15;267(8):5467–5473. [PubMed] [Google Scholar]
  18. Hunziker W., Mellman I. Expression of macrophage-lymphocyte Fc receptors in Madin-Darby canine kidney cells: polarity and transcytosis differ for isoforms with or without coated pit localization domains. J Cell Biol. 1989 Dec;109(6 Pt 2):3291–3302. doi: 10.1083/jcb.109.6.3291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Indik Z., Kelly C., Chien P., Levinson A. I., Schreiber A. D. Human Fc gamma RII, in the absence of other Fc gamma receptors, mediates a phagocytic signal. J Clin Invest. 1991 Nov;88(5):1766–1771. doi: 10.1172/JCI115496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Irving B. A., Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991 Mar 8;64(5):891–901. doi: 10.1016/0092-8674(91)90314-o. [DOI] [PubMed] [Google Scholar]
  21. Jin Y. J., Clayton L. K., Howard F. D., Koyasu S., Sieh M., Steinbrich R., Tarr G. E., Reinherz E. L. Molecular cloning of the CD3 eta subunit identifies a CD3 zeta-related product in thymus-derived cells. Proc Natl Acad Sci U S A. 1990 May;87(9):3319–3323. doi: 10.1073/pnas.87.9.3319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Keegan A. D., Paul W. E. Multichain immune recognition receptors: similarities in structure and signaling pathways. Immunol Today. 1992 Feb;13(2):63–68. doi: 10.1016/0167-5699(92)90136-U. [DOI] [PubMed] [Google Scholar]
  23. Kinet J. P. Antibody-cell interactions: Fc receptors. Cell. 1989 May 5;57(3):351–354. doi: 10.1016/0092-8674(89)90910-0. [DOI] [PubMed] [Google Scholar]
  24. Kroczek R. A., Gunter K. C., Germain R. N., Shevach E. M. Thy-1 functions as a signal transduction molecule in T lymphocytes and transfected B lymphocytes. Nature. 1986 Jul 10;322(6075):181–184. doi: 10.1038/322181a0. [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., Yu G., Phillips J. H. Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Nature. 1989 Dec 14;342(6251):803–805. doi: 10.1038/342803a0. [DOI] [PubMed] [Google Scholar]
  27. Letourneur F., Klausner R. D. Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3 epsilon. Science. 1992 Jan 3;255(5040):79–82. doi: 10.1126/science.1532456. [DOI] [PubMed] [Google Scholar]
  28. Letourneur F., Klausner R. D. T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8905–8909. doi: 10.1073/pnas.88.20.8905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Liao F., Shin H. S., Rhee S. G. Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3659–3663. doi: 10.1073/pnas.89.8.3659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mellman I. Relationships between structure and function in the Fc receptor family. Curr Opin Immunol. 1988 Sep-Oct;1(1):16–25. doi: 10.1016/0952-7915(88)90046-5. [DOI] [PubMed] [Google Scholar]
  31. Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
  32. Miettinen H. M., Matter K., Hunziker W., Rose J. K., Mellman I. Fc receptor endocytosis is controlled by a cytoplasmic domain determinant that actively prevents coated pit localization. J Cell Biol. 1992 Feb;116(4):875–888. doi: 10.1083/jcb.116.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Miettinen H. M., Rose J. K., Mellman I. Fc receptor isoforms exhibit distinct abilities for coated pit localization as a result of cytoplasmic domain heterogeneity. Cell. 1989 Jul 28;58(2):317–327. doi: 10.1016/0092-8674(89)90846-5. [DOI] [PubMed] [Google Scholar]
  34. Moingeon P., Lucich J. L., McConkey D. J., Letourneur F., Malissen B., Kochan J., Chang H. C., Rodewald H. R., Reinherz E. L. CD3 zeta dependence of the CD2 pathway of activation in T lymphocytes and natural killer cells. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1492–1496. doi: 10.1073/pnas.89.4.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Odin J. A., Edberg J. C., Painter C. J., Kimberly R. P., Unkeless J. C. Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor. Science. 1991 Dec 20;254(5039):1785–1788. doi: 10.1126/science.1837175. [DOI] [PubMed] [Google Scholar]
  36. Ostergaard H. L., Kane K. P., Mescher M. F., Clark W. R. Cytotoxic T lymphocyte mediated lysis without release of serine esterase. Nature. 1987 Nov 5;330(6143):71–72. doi: 10.1038/330071a0. [DOI] [PubMed] [Google Scholar]
  37. Park D. J., Min H. K., Rhee S. G. IgE-induced tyrosine phosphorylation of phospholipase C-gamma 1 in rat basophilic leukemia cells. J Biol Chem. 1991 Dec 25;266(36):24237–24240. [PubMed] [Google Scholar]
  38. Qiu W. Q., de Bruin D., Brownstein B. H., Pearse R., Ravetch J. V. Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination. Science. 1990 May 11;248(4956):732–735. doi: 10.1126/science.2139735. [DOI] [PubMed] [Google Scholar]
  39. Ra C., Jouvin M. H., Kinet J. P. Complete structure of the mouse mast cell receptor for IgE (Fc epsilon RI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells. J Biol Chem. 1989 Sep 15;264(26):15323–15327. [PubMed] [Google Scholar]
  40. Rabinovitch P. S., June C. H., Grossmann A., Ledbetter J. A. Heterogeneity among T cells in intracellular free calcium responses after mitogen stimulation with PHA or anti-CD3. Simultaneous use of indo-1 and immunofluorescence with flow cytometry. J Immunol. 1986 Aug 1;137(3):952–961. [PubMed] [Google Scholar]
  41. Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [PubMed] [Google Scholar]
  42. Reth M. Antigen receptor tail clue. Nature. 1989 Mar 30;338(6214):383–384. doi: 10.1038/338383b0. [DOI] [PubMed] [Google Scholar]
  43. Romeo C., Amiot M., Seed B. Sequence requirements for induction of cytolysis by the T cell antigen/Fc receptor zeta chain. Cell. 1992 Mar 6;68(5):889–897. doi: 10.1016/0092-8674(92)90032-8. [DOI] [PubMed] [Google Scholar]
  44. Romeo C., Seed B. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides. Cell. 1991 Mar 8;64(5):1037–1046. doi: 10.1016/0092-8674(91)90327-u. [DOI] [PubMed] [Google Scholar]
  45. Samelson L. E., Harford J. B., Klausner R. D. Identification of the components of the murine T cell antigen receptor complex. Cell. 1985 Nov;43(1):223–231. doi: 10.1016/0092-8674(85)90027-3. [DOI] [PubMed] [Google Scholar]
  46. Schmitt-Verhulst A. M., Guimezanes A., Boyer C., Poenie M., Tsien R., Buferne M., Hua C., Leserman L. Pleiotropic loss of activation pathways in a T-cell receptor alpha-chain deletion variant of a cytolytic T-cell clone. Nature. 1987 Feb 12;325(6105):628–631. doi: 10.1038/325628a0. [DOI] [PubMed] [Google Scholar]
  47. Sefton B. M., Campbell M. A. The role of tyrosine protein phosphorylation in lymphocyte activation. Annu Rev Cell Biol. 1991;7:257–274. doi: 10.1146/annurev.cb.07.110191.001353. [DOI] [PubMed] [Google Scholar]
  48. Shen L., Graziano R. F., Fanger M. W. The functional properties of Fc gamma RI, II and III on myeloid cells: a comparative study of killing of erythrocytes and tumor cells mediated through the different Fc receptors. Mol Immunol. 1989 Oct;26(10):959–969. doi: 10.1016/0161-5890(89)90114-4. [DOI] [PubMed] [Google Scholar]
  49. Stengelin S., Stamenkovic I., Seed B. Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning. EMBO J. 1988 Apr;7(4):1053–1059. doi: 10.1002/j.1460-2075.1988.tb02913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Stuart S. G., Simister N. E., Clarkson S. B., Kacinski B. M., Shapiro M., Mellman I. Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium. EMBO J. 1989 Dec 1;8(12):3657–3666. doi: 10.1002/j.1460-2075.1989.tb08540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Trenn G., Taffs R., Hohman R., Kincaid R., Shevach E. M., Sitkovsky M. Biochemical characterization of the inhibitory effect of CsA on cytolytic T lymphocyte effector functions. J Immunol. 1989 Jun 1;142(11):3796–3802. [PubMed] [Google Scholar]
  52. Trenn G., Takayama H., Sitkovsky M. V. Exocytosis of cytolytic granules may not be required for target cell lysis by cytotoxic T-lymphocytes. Nature. 1987 Nov 5;330(6143):72–74. doi: 10.1038/330072a0. [DOI] [PubMed] [Google Scholar]
  53. 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]
  54. Wegener A. M., Letourneur F., Hoeveler A., Brocker T., Luton F., Malissen B. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Cell. 1992 Jan 10;68(1):83–95. doi: 10.1016/0092-8674(92)90208-t. [DOI] [PubMed] [Google Scholar]
  55. Weiss A., Stobo J. D. Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J Exp Med. 1984 Nov 1;160(5):1284–1299. doi: 10.1084/jem.160.5.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Weissman A. M., Baniyash M., Hou D., Samelson L. E., Burgess W. H., Klausner R. D. Molecular cloning of the zeta chain of the T cell antigen receptor. Science. 1988 Feb 26;239(4843):1018–1021. doi: 10.1126/science.3278377. [DOI] [PubMed] [Google Scholar]
  57. Yeh E. T., Reiser H., Daley J., Rock K. L. Stimulation of T cells via the TAP molecule, a member in a family of activating proteins encoded in the Ly-6 locus. J Immunol. 1987 Jan 1;138(1):91–97. [PubMed] [Google Scholar]
  58. Yokoyama W. M., Shevach E. M. T cell activation via cell-surface antigens other than the CD3/T cell receptor complex. Year Immunol. 1989;4:110–146. [PubMed] [Google Scholar]
  59. Young J. D., Clark W. R., Liu C. C., Cohn Z. A. A calcium- and perforin-independent pathway of killing mediated by murine cytolytic lymphocytes. J Exp Med. 1987 Dec 1;166(6):1894–1899. doi: 10.1084/jem.166.6.1894. [DOI] [PMC free article] [PubMed] [Google Scholar]

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