Abstract
The Fc receptors (FcR), which belong to the immunoglobulin (Ig) superfamily, bind to specific Ig isotypes with varying affinities triggering complex immune defense responses. Several of the FcR that lack signaling motifs in their cytoplasmic domains rely on associated subunits to transmit signals. Two classes of FcR that bind the Fc portion of IgG, Fc gamma RI, and Fc gamma RIIIa associate with a subunit shared among several FcR, the gamma chain, which is involved in receptor expression and signal transduction. In this report, we propose that a novel role for gamma chain is to enhance the affinity of Fc gamma R for ligand. Our findings demonstrate that Fc gamma RI requires gamma -chain association to attain high affinity binding for monomeric IgG, and suggest that the intermediate binding affinity of the Fc gamma RIIIa isoform results from its association with gamma chain. The affinity increase conferred by gamma chain appears to be mediated through the transmembrane domain of the Fc gamma R, with no requirement for the cytoplasmic domain of the receptor.
Full Text
The Full Text of this article is available as a PDF (777.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allen J. M., Seed B. Isolation and expression of functional high-affinity Fc receptor complementary DNAs. Science. 1989 Jan 20;243(4889):378–381. doi: 10.1126/science.2911749. [DOI] [PubMed] [Google Scholar]
- Anderson C. L., Abraham G. N. Characterization of the Fc receptor for IgG on a human macrophage cell line, U937. J Immunol. 1980 Dec;125(6):2735–2741. [PubMed] [Google Scholar]
- 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]
- Ernst L. K., Duchemin A. M., Anderson C. L. Association of the high-affinity receptor for IgG (Fc gamma RI) with the gamma subunit of the IgE receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6023–6027. doi: 10.1073/pnas.90.13.6023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hulett M. D., Osman N., McKenzie I. F., Hogarth P. M. Chimeric Fc receptors identify functional domains of the murine high affinity receptor for IgG. J Immunol. 1991 Sep 15;147(6):1863–1868. [PubMed] [Google Scholar]
- Kishimoto T., Akira S., Taga T. Interleukin-6 and its receptor: a paradigm for cytokines. Science. 1992 Oct 23;258(5082):593–597. doi: 10.1126/science.1411569. [DOI] [PubMed] [Google Scholar]
- Kurosaki T., Gander I., Ravetch J. V. A subunit common to an IgG Fc receptor and the T-cell receptor mediates assembly through different interactions. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3837–3841. doi: 10.1073/pnas.88.9.3837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Küster H., Thompson H., Kinet J. P. Characterization and expression of the gene for the human Fc receptor gamma subunit. Definition of a new gene family. J Biol Chem. 1990 Apr 15;265(11):6448–6452. [PubMed] [Google Scholar]
- Maliszewski C. R., March C. J., Schoenborn M. A., Gimpel S., Shen L. Expression cloning of a human Fc receptor for IgA. J Exp Med. 1990 Dec 1;172(6):1665–1672. doi: 10.1084/jem.172.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nicola N. A., Metcalf D. Subunit promiscuity among hemopoietic growth factor receptors. Cell. 1991 Oct 4;67(1):1–4. doi: 10.1016/0092-8674(91)90564-f. [DOI] [PubMed] [Google Scholar]
- Noguchi M., Nakamura Y., Russell S. M., Ziegler S. F., Tsang M., Cao X., Leonard W. J. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science. 1993 Dec 17;262(5141):1877–1880. doi: 10.1126/science.8266077. [DOI] [PubMed] [Google Scholar]
- Noguchi M., Nakamura Y., Russell S. M., Ziegler S. F., Tsang M., Cao X., Leonard W. J. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science. 1993 Dec 17;262(5141):1877–1880. doi: 10.1126/science.8266077. [DOI] [PubMed] [Google Scholar]
- Pfefferkorn L. C., Yeaman G. R. Association of IgA-Fc receptors (Fc alpha R) with Fc epsilon RI gamma 2 subunits in U937 cells. Aggregation induces the tyrosine phosphorylation of gamma 2. J Immunol. 1994 Oct 1;153(7):3228–3236. [PubMed] [Google Scholar]
- Ra C., Jouvin M. H., Blank U., Kinet J. P. A macrophage Fc gamma receptor and the mast cell receptor for IgE share an identical subunit. Nature. 1989 Oct 26;341(6244):752–754. doi: 10.1038/341752a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Russell S. M., Keegan A. D., Harada N., Nakamura Y., Noguchi M., Leland P., Friedmann M. C., Miyajima A., Puri R. K., Paul W. E. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science. 1993 Dec 17;262(5141):1880–1883. doi: 10.1126/science.8266078. [DOI] [PubMed] [Google Scholar]
- Sears D. W., Osman N., Tate B., McKenzie I. F., Hogarth P. M. Molecular cloning and expression of the mouse high affinity Fc receptor for IgG. J Immunol. 1990 Jan 1;144(1):371–378. [PubMed] [Google Scholar]
- Unkeless J. C., Eisen H. N. Binding of monomeric immunoglobulins to Fc receptors of mouse macrophages. J Exp Med. 1975 Dec 1;142(6):1520–1533. doi: 10.1084/jem.142.6.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yin T., Taga T., Tsang M. L., Yasukawa K., Kishimoto T., Yang Y. C. Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction. J Immunol. 1993 Sep 1;151(5):2555–2561. [PubMed] [Google Scholar]
- van de Winkel J. G., Capel P. J. Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. Immunol Today. 1993 May;14(5):215–221. doi: 10.1016/0167-5699(93)90166-I. [DOI] [PubMed] [Google Scholar]