Fc epsilon receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin S-dependent pathway of MHC class II presentation - PubMed (original) (raw)
. 1998 Sep 15;161(6):2731-9.
Affiliations
- PMID: 9743330
Fc epsilon receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin S-dependent pathway of MHC class II presentation
D Maurer et al. J Immunol. 1998.
Abstract
In this study, we elucidate the Fc epsilon RI-mediated Ag uptake and presentation mechanisms of dendritic cells (DC). We found that Fc epsilon RI-bound IgE, after polyvalent but not after monovalent ligation, is efficiently internalized into acidic, proteolytic compartments, degraded, and delivered into organelles containing MHC class II, HLA-DM, and lysosomal proteins. To follow the fate of the fragmented ligand, we sought to interfere with invariant chain (Ii) degradation, a process critical for peptide loading of nascent MHC class II molecules. We found DC to express cathepsin (Cat) S, a cysteine protease involved in Ii processing by B cells. Exposure of DC to a specific, active-site inhibitor of Cat S resulted in the loss of anti-Cat S immunoreactivity, led to the appearance of an N-terminal Ii remnant, and decreased the export of newly synthesized MHC class II to the DC surface. Furthermore, inactivation of Cat S as well as blockade of protein neosynthesis by cycloheximide strongly reduced IgE/Fc epsilon RI-mediated Ag presentation by DC. Thus, multimeric ligands of Fc epsilon RI, instead of being delivered into a recycling MHC class H pathway, are channeled efficiently into MIIC (MHC class II compartment)-like organelles of DC, in which Cat S-dependent Ii processing and peptide loading of newly synthesized MHC class II molecules occur. This IgE/Fc epsilon RI-dependent signaling pathway in DC may be a particularly effective route for immunization and a promising target for interfering with the early steps of allergen presentation.
Similar articles
- MHC class II compartments and the kinetics of antigen presentation in activated mouse spleen dendritic cells.
Kleijmeer MJ, Ossevoort MA, van Veen CJ, van Hellemond JJ, Neefjes JJ, Kast WM, Melief CJ, Geuze HJ. Kleijmeer MJ, et al. J Immunol. 1995 Jun 1;154(11):5715-24. J Immunol. 1995. PMID: 7751623 - Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation.
Maurer D, Fiebiger S, Ebner C, Reininger B, Fischer GF, Wichlas S, Jouvin MH, Schmitt-Egenolf M, Kraft D, Kinet JP, Stingl G. Maurer D, et al. J Immunol. 1996 Jul 15;157(2):607-16. J Immunol. 1996. PMID: 8752908 - MHC class II antigen processing in B cells: accelerated intracellular targeting of antigens.
Cheng PC, Steele CR, Gu L, Song W, Pierce SK. Cheng PC, et al. J Immunol. 1999 Jun 15;162(12):7171-80. J Immunol. 1999. PMID: 10358163 - Quality control of MHC class II associated peptides by HLA-DM/H2-M.
Vogt AB, Arndt SO, Hämmerling GJ, Kropshofer H. Vogt AB, et al. Semin Immunol. 1999 Dec;11(6):391-403. doi: 10.1006/smim.1999.0197. Semin Immunol. 1999. PMID: 10625593 Review. - Intracellular organelles involved in antigen processing and the binding of peptides to class II MHC molecules.
Harding CV. Harding CV. Semin Immunol. 1995 Dec;7(6):355-60. doi: 10.1006/smim.1995.0040. Semin Immunol. 1995. PMID: 8775461 Review.
Cited by
- Controlling Antigen Fate in Therapeutic Cancer Vaccines by Targeting Dendritic Cell Receptors.
Wijfjes Z, van Dalen FJ, Le Gall CM, Verdoes M. Wijfjes Z, et al. Mol Pharm. 2023 Oct 2;20(10):4826-4847. doi: 10.1021/acs.molpharmaceut.3c00330. Epub 2023 Sep 18. Mol Pharm. 2023. PMID: 37721387 Free PMC article. Review. - Transfer learning efficiently maps bone marrow cell types from mouse to human using single-cell RNA sequencing.
Stumpf PS, Du X, Imanishi H, Kunisaki Y, Semba Y, Noble T, Smith RCG, Rose-Zerili M, West JJ, Oreffo ROC, Farrahi K, Niranjan M, Akashi K, Arai F, MacArthur BD. Stumpf PS, et al. Commun Biol. 2020 Dec 4;3(1):736. doi: 10.1038/s42003-020-01463-6. Commun Biol. 2020. PMID: 33277618 Free PMC article. - The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab.
Gasser P, Tarchevskaya SS, Guntern P, Brigger D, Ruppli R, Zbären N, Kleinboelting S, Heusser C, Jardetzky TS, Eggel A. Gasser P, et al. Nat Commun. 2020 Jan 8;11(1):165. doi: 10.1038/s41467-019-13815-w. Nat Commun. 2020. PMID: 31913280 Free PMC article. - Treatment of estrogen-induced dermatitis with omalizumab.
Ocana JA, Bell MC, Heskett JB, Baker WH, Mousdicas N, Turner MJ. Ocana JA, et al. JAAD Case Rep. 2019 May 25;5(6):481-483. doi: 10.1016/j.jdcr.2019.03.007. eCollection 2019 Jun. JAAD Case Rep. 2019. PMID: 31193571 Free PMC article. No abstract available. - Subcutaneous immunotherapy induces alterations in monocytes and dendritic cells homeostasis in allergic rhinitis patients.
Sousa L, Martín-Sierra C, Pereira C, Loureiro G, Tavares B, Pedreiro S, Martinho A, Paiva A. Sousa L, et al. Allergy Asthma Clin Immunol. 2018 Nov 15;14:45. doi: 10.1186/s13223-018-0271-8. eCollection 2018. Allergy Asthma Clin Immunol. 2018. PMID: 30459816 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Research Materials
Miscellaneous