Inhibition of antigen-induced mediator release from IgE-sensitized cells by a monoclonal anti-Fc epsilon RI alpha-chain receptor antibody: implications for the involvement of the membrane-proximal alpha-chain region in Fc epsilon RI-mediated cell activation

The Journal of Immunology : Official Journal of the American Association of Immunologists
A NechanskyFranz Kricek

Abstract

The interaction between human IgE and its high affinity receptor, FcepsilonRI, is a critical event in mediating the allergic response. Aggregation of the alpha-chain of FcepsilonRI (FcepsilonRIalpha) occurs via cross-linking of receptor-bound IgE by Ag, resulting in cell activation and the release of mediators of hypersensitivity. Recently, we mapped the epitopes of two anti-FcepsilonRIalpha mAbs, 15/1 and 5H5F8. In contrast to 15/1, mAb 5H5F8 does not inhibit IgE binding to FcepsilonRIalpha. Here we demonstrate both 5H5F8 binding to FcepsilonRI(+) cells as well as a high level of IgE binding to 5H5F8-saturated cells. At the same time 5H5F8 strongly inhibits hexosaminidase release and Ca(2+) flux after Ag triggering from human IgE-sensitized RBL-2H3 cells stably transfected with human FcepsilonRIalpha. Further, 5H5F8 and its Fab inhibit sulfidoleukotriene and histamine release from primary human peripheral blood leukocytes, including cells bearing endogenous IGE: Furthermore, we confirm that 5H5F8 maps to a linear peptide sequence in close proximity to the cell membrane. Two chemically synthesized peptides containing the 5H5F8 epitope sequence PREKY were selected for detailed analysis of 5H5F8 and 5H5F8 Fab binding and were fou...Continue Reading

References

Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S Y MaoH Metzger
May 1, 1992·The Journal of Experimental Medicine·B WangG Stingl
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A ShimizuP Leder
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·P J MillardC Fewtrell
Feb 1, 1995·The Journal of Clinical Investigation·M DaëronW H Fridman
Dec 2, 1993·Nature·B J Sutton, H J Gould
May 1, 1993·Immunology Today·J G van de Winkel, P J Capel
May 1, 1993·Immunology Today·M A Beaven, H Metzger
Jan 1, 1996·Annual Review of Biophysics and Biomolecular Structure·D Holowka, B Baird
Feb 14, 1997·The Journal of Biological Chemistry·K A FieldB Baird
Oct 23, 1997·The Journal of Experimental Medicine·T J FlemingJ P Kinet
Jan 6, 1999·Cell·S C GarmanT S Jardetzky
Jan 9, 1999·The Journal of Biological Chemistry·K A FieldB Baird
Feb 18, 1999·Current Opinion in Chemical Biology·E D SheetsB Baird
May 1, 1999·The Journal of Biological Chemistry·M D HulettP M Hogarth
Jun 8, 1999·Annual Review of Immunology·J P Kinet
Jan 13, 2000·Current Opinion in Immunology·A M Scharenberg
Mar 29, 2000·The Journal of Biological Chemistry·R L YauchM E Hemler

❮ Previous
Next ❯

Citations

Dec 26, 2002·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Sep 11, 2007·Chembiochem : a European Journal of Chemical Biology·Carsten PetersKlaus Weigand
Nov 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomasz BobrzynskiSylvia M Miescher
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshiyuki KubotaHajime Karasuyama
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jim J C SheuTse-Wen Chang
Nov 1, 2007·Expert Opinion on Medical Diagnostics·Michael J BaumannMonique Vogel
Jul 16, 2008·Chemical Biology & Drug Design·Angeliki BukuJoseph A Price
Jul 28, 2004·Journal of Molecular Biology·Monique VogelBeda M Stadler
Aug 18, 2009·Journal of Molecular Biology·Alexander EggelMonique Vogel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody Specificity

Antibodies produced by B cells are highly specific for antigen as a result of random gene recombination and somatic hypermutation and affinity maturation. As the main effector of the humoral immune system, antibodies can neutralize foreign cells. Find the latest research on antibody specificity here.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Basophils

Basophils are myeloid cells with a high affinity IgE receptor and is involved in inflammatory responses during allergy. Discover the latest research on Basophils here.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.