Galli, S. J. & Tsai, M. IgE and mast cells in allergic disease. Nat. Med. 18, 693â704 (2012).
McDonnell, J. M., Dhaliwal, B., Sutton, B. J. & Gould, H. J. IgE, IgE receptors and anti-IgE biologics: protein structures and mechanisms of action. Annu. Rev. Immunol. 41, 255â275 (2023).
Kinet, J. P. The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annu. Rev. Immunol. 17, 931â972 (1999).
Martin, A. M., Kulski, J. K., Witt, C., Pontarotti, P. & Christiansen, F. T. Leukocyte Ig-like receptor complex (LRC) in mice and men. Trends Immunol. 23, 81â88 (2002).
Humphrey, M. B., Lanier, L. L. & Nakamura, M. C. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol. Rev. 208, 50â65 (2005).
Nimmerjahn, F. & Ravetch, J. V. Fcgamma receptors as regulators of immune responses. Nat. Rev. Immunol. 8, 34â47 (2008).
Hogarth, P. M. & Pietersz, G. A. Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond. Nat. Rev. Drug Discov. 11, 311â331 (2012).
Brandsma, A. M., Hogarth, P. M., Nimmerjahn, F. & Leusen, J. H. Clarifying the confusion between cytokine and Fc receptor âcommon gamma chainâ. Immunity 45, 225â226 (2016).
Bruhns, P. & Jonsson, F. Mouse and human FcR effector functions. Immunol. Rev. 268, 25â51 (2015).
Blank, U. et al. Complete structure and expression in transfected cells of high affinity IgE receptor. Nature 337, 187â189 (1989).
Miller, L., Blank, U., Metzger, H. & Kinet, J. P. Expression of high-affinity binding of human immunoglobulin E by transfected cells. Science 244, 334â337 (1989).
Alber, G., Miller, L., Jelsema, C. L., Varin-Blank, N. & Metzger, H. Structure-function relationships in the mast cell high affinity receptor for IgE. Role of the cytoplasmic domains and of the beta subunit. J. Biol. Chem. 266, 22613â22620 (1991).
Lin, S., Cicala, C., Scharenberg, A. M. & Kinet, J. P. The FcεRIβ subunit functions as an amplifier of FcεRIγ-mediated cell activation signals. Cell 85, 985â995 (1996).
Turner, H. & Kinet, J. P. Signalling through the high-affinity IgE receptor FcεRI. Nature 402, B24âB30 (1999).
Kraft, S. & Kinet, J. P. New developments in FcεRI regulation, function and inhibition. Nat. Rev. Immunol. 7, 365â378 (2007).
Underhill, D. M. & Goodridge, H. S. The many faces of ITAMs. Trends Immunol. 28, 66â73 (2007).
Mócsai, A., Ruland, J. & Tybulewicz, V. L. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat. Rev. Immunol. 10, 387â402 (2010).
Orloff, D. G., Ra, C. S., Frank, S. J., Klausner, R. D. & Kinet, J. P. Family of disulphide-linked dimers containing the ζ and η chains of the T-cell receptor and the gamma chain of Fc receptors. Nature 347, 189â191 (1990).
Garman, S. C., Wurzburg, B. A., Tarchevskaya, S. S., Kinet, J. P. & Jardetzky, T. S. Structure of the Fc fragment of human IgE bound to its high-affinity receptor FcεRIα. Nature 406, 259â266 (2000).
Holdom, M. D. et al. Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor FcÉRI. Nat. Struct. Mol. Biol. 18, 571â576 (2011).
Drinkwater, N. et al. Human immunoglobulin E flexes between acutely bent and extended conformations. Nat. Struct. Mol. Biol. 21, 397â404 (2014).
Blank, U., Ra, C. S. & Kinet, J. P. Characterization of truncated alpha chain products from human, rat, and mouse high affinity receptor for immunoglobulin E. J. Biol. Chem. 266, 2639â2646 (1991).
Passante, E. & Frankish, N. The RBL-2H3 cell line: its provenance and suitability as a model for the mast cell. Inflamm. Res. 58, 737â745 (2009).
Mattiola, I., Mantovani, A. & Locati, M. The tetraspan MS4A family in homeostasis, immunity, and disease. Trends Immunol. 42, 764â781 (2021).
Rougé, L. et al. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab. Science 367, 1224â1230 (2020).
Kumar, A., Planchais, C., Fronzes, R., Mouquet, H. & Reyes, N. Binding mechanisms of therapeutic antibodies to human CD20. Science 369, 793â799 (2020).
Singleton, T. E., Platzer, B., Dehlink, E. & Fiebiger, E. The first transmembrane region of the beta-chain stabilizes the tetrameric Fc epsilon RI complex. Mol. Immunol. 46, 2333â2339 (2009).
Rashid, A. et al. Assessing the role of Asp 194 in the transmembrane domains of the alpha-chain of the high-affinity receptor complex for immunoglobulin E in signal transduction. Mol. Immunol. 48, 128â136 (2010).
Blazquez-Moreno, A. et al. Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules. Proc. Natl Acad. Sci. USA 114, E5645âE5654 (2017).
Kuster, 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. 265, 6448â6452 (1990).
Wines, B. D., Trist, H. M., Ramsland, P. A. & Hogarth, P. M. A common site of the Fc receptor gamma subunit interacts with the unrelated immunoreceptors FcαRI and FcεRI. J. Biol. Chem. 281, 17108â17113 (2006).
Travers, T. et al. Combinatorial diversity of Syk recruitment driven by its multivalent engagement with FcεRIγ. Mol. Biol. Cell 30, 2331â2347 (2019).
Bax, H. J., Bowen, H., Dodev, T. S., Sutton, B. J. & Gould, H. J. Mechanism of the antigen-independent cytokinergic SPE-7 IgE activation of human mast cells in vitro. Sci. Rep. 5, 9538 (2015).
Hibbs, M. L. et al. Mechanisms for regulating expression of membrane isoforms of Fc gamma RIII (CD16). Science 246, 1608â1611 (1989).
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. USA 88, 3837â3841 (1991).
Wines, B. D., Trist, H. M., Monteiro, R. C., Van Kooten, C. & Hogarth, P. M. Fc receptor γ chain residues at the interface of the cytoplasmic and transmembrane domains affect association with FcαRI, surface expression, and function. J. Biol. Chem. 279, 26339â26345 (2004).
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. 153, 3228â3236 (1994).
Morton, H. C. et al. Functional association between the human myeloid immunoglobulin A Fc receptor (CD89) and FcR gamma chain. Molecular basis for CD89/FcR gamma chain association. J. Biol. Chem. 270, 29781â29787 (1995).
Fewtrell, C., Mohr, F. C., Ryan, T. A. & Millard, P. J. in Novartis Foundation Symposia Ciba Foundation Symposium 147 â IgE, Mast Cells and the Allergic Response (eds Chadwick, D. J. et al.) 114â132 (Wiley, 1989).
Metzger, H. et al. The receptor with high affinity for immunoglobulin E. Annu. Rev. Immunol. 4, 419â470 (1986).
Dong, D. et al. Structural basis of assembly of the human T cell receptor-CD3 complex. Nature 573, 546â552 (2019).
Chen, Y. et al. Cholesterol inhibits TCR signaling by directly restricting TCR-CD3 core tunnel motility. Mol. Cell 82, 1278â1287 (2022).
SuÅ¡ac, L. et al. Structure of a fully assembled tumor-specific T cell receptor ligated by pMHC. Cell 185, 3201â3213 (2022).
Saotome, K. et al. Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM. Nat. Commun. 14, 2401 (2023).
Xin, W. et al. Structures of human γδ T cell receptorâCD3 complex. Nature https://doi.org/10.1038/s41586-024-07439-4 (2024).
Sheets, E. D., Holowka, D. & Baird, B. Critical role for cholesterol in Lyn-mediated tyrosine phosphorylation of FcεRI and their association with detergent-resistant membranes. J. Cell Biol. 145, 877â887 (1999).
Curnow, S. J., Boyer, C., Buferne, M. & Schmitt-Verhulst, A. M. TCR-associated ζ-FcεRIγ heterodimers on CD4âCD8â NK1.1+ T cells selected by specific class I MHC antigen. Immunity 3, 427â438 (1995).
Enyedy, E. J. et al. Fc epsilon receptor type I gamma chain replaces the deficient T cell receptor zeta chain in T cells of patients with systemic lupus erythematosus. Arthritis Rheum. 44, 1114â1121 (2001).
Krishnan, S., Warke, V. G., Nambiar, M. P., Tsokos, G. C. & Farber, D. L. The FcR gamma subunit and Syk kinase replace the CD3 zeta-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells. J. Immunol. 170, 4189â4195 (2003).
Lanier, L. L. Up on the tightrope: natural killer cell activation and inhibition. Nat. Immunol. 9, 495â502 (2008).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290â296 (2017).
Wang, N. et al. Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates. Cell 184, 370â383 (2021).
Pettersen, E. F. et al. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605â1612 (2004).
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583â589 (2021).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486â501 (2010).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213â221 (2010).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70â82 (2021).
Bawazir, M., Amponnawarat, A., Hui, Y., Oskeritzian, C. A. & Ali, H. Inhibition of MRGPRX2 but not FcεRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist. Front. Immunol. 13, 1033794 (2022).
