Signaling through mutants of the IgA receptor CD89 and consequences for Fc receptor gamma-chain interaction

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jantine E BakemaJeanette H W Leusen

Abstract

The prototypic receptor for IgA (FcalphaRI, CD89) is expressed on myeloid cells and can trigger phagocytosis, tumor cell lysis, and release of inflammatory mediators. The functions of FcalphaRI and activating receptors for IgG (FcgammaRI and FcgammaRIII) are dependent on the FcR gamma-chain dimer. This study increases our understanding of the molecular basis of the FcalphaRI-FcR gamma-chain transmembrane interaction, which is distinct from that of other activatory FcRs. FcalphaRI is unique in its interaction with the common FcR gamma-chain, because it is based on a positively charged residue at position 209, which associates with a negatively charged amino acid of FcR gamma-chain. We explored the importance of the position of this positive charge within human FcalphaRI for FcR gamma-chain association and FcalphaRI functioning with the use of site-directed mutagenesis. In an FcalphaRI R209L/A213H mutant, which represents a vertical relocation of the positive charge, proximal and distal FcR gamma-chain-dependent functions, such as calcium flux, MAPK phosphorylation, and IL-2 release, were similar to those of wild-type FcalphaRI. A lateral transfer of the positive charge, however, completely abrogated FcR gamma-chain-dependent fun...Continue Reading

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Citations

Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael DechantThomas Valerius
Apr 23, 2010·European Journal of Immunology·Jantine E BakemaJeanette H W Leusen
Jun 22, 2011·MAbs·Jantine E Bakema, Marjolein van Egmond
Oct 27, 2015·Immunological Reviews·Esil AleydMarjolein van Egmond
Dec 27, 2016·European Journal of Clinical Investigation·Marieke H Heineke, Marjolein van Egmond
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chigusa NakahashiAkira Shibuya
Apr 27, 2012·European Journal of Immunology·Marielle A OttenMarjolein van Egmond
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jantine E BakemaJeanette H W Leusen
Dec 14, 2007·Autoimmunity·Elizabeth E BrownRobert P Kimberly
Oct 27, 2015·Immunological Reviews·Alicia M ChenowethP Mark Hogarth
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marielle A OttenMarjolein van Egmond

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