A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria

The alpha-Gal epitope (α-Gal) with the determining element galactose-α1,3-galactose can lead to clinically relevant allergic reactions and rejections in xenotransplantation. These immune reactions can develop because humans are devoid of this carbohydrate due to evolutionary loss of the enzyme α1,3-...

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Main Authors: Luisa Kreft, Aloys Schepers, Miriam Hils, Kyra Swiontek, Andrew Flatley, Robert Janowski, Mohammadali Khan Mirzaei, Michael Dittmar, Neera Chakrapani, Mahesh S. Desai, Stefanie Eyerich, Li Deng, Dierk Niessing, Konrad Fischer, Regina Feederle, Simon Blank, Carsten B. Schmidt-Weber, Christiane Hilger, Tilo Biedermann, Caspar Ohnmacht
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.958952/full
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author Luisa Kreft
Aloys Schepers
Miriam Hils
Kyra Swiontek
Andrew Flatley
Robert Janowski
Mohammadali Khan Mirzaei
Mohammadali Khan Mirzaei
Michael Dittmar
Neera Chakrapani
Mahesh S. Desai
Mahesh S. Desai
Stefanie Eyerich
Li Deng
Li Deng
Dierk Niessing
Konrad Fischer
Regina Feederle
Simon Blank
Carsten B. Schmidt-Weber
Carsten B. Schmidt-Weber
Christiane Hilger
Tilo Biedermann
Caspar Ohnmacht
author_facet Luisa Kreft
Aloys Schepers
Miriam Hils
Kyra Swiontek
Andrew Flatley
Robert Janowski
Mohammadali Khan Mirzaei
Mohammadali Khan Mirzaei
Michael Dittmar
Neera Chakrapani
Mahesh S. Desai
Mahesh S. Desai
Stefanie Eyerich
Li Deng
Li Deng
Dierk Niessing
Konrad Fischer
Regina Feederle
Simon Blank
Carsten B. Schmidt-Weber
Carsten B. Schmidt-Weber
Christiane Hilger
Tilo Biedermann
Caspar Ohnmacht
author_sort Luisa Kreft
collection DOAJ
description The alpha-Gal epitope (α-Gal) with the determining element galactose-α1,3-galactose can lead to clinically relevant allergic reactions and rejections in xenotransplantation. These immune reactions can develop because humans are devoid of this carbohydrate due to evolutionary loss of the enzyme α1,3-galactosyltransferase (GGTA1). In addition, up to 1% of human IgG antibodies are directed against α-Gal, but the stimulus for the induction of anti-α-Gal antibodies is still unclear. Commensal bacteria have been suggested as a causal factor for this induction as α-Gal binding tools such as lectins were found to stain cultivated bacteria isolated from the intestinal tract. Currently available tools for the detection of the definite α-Gal epitope, however, are cross-reactive, or have limited affinity and, hence, offer restricted possibilities for application. In this study, we describe a novel monoclonal IgG1 antibody (27H8) specific for the α-Gal epitope. The 27H8 antibody was generated by immunization of Ggta1 knockout mice and displays a high affinity towards synthetic and naturally occurring α-Gal in various applications. Using this novel tool, we found that intestinal bacteria reported to be α-Gal positive cannot be stained with 27H8 questioning whether commensal bacteria express the native α-Gal epitope at all.
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spelling doaj.art-252b4a8f311446508d50f98a1e9b29b02022-12-22T01:39:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.958952958952A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteriaLuisa Kreft0Aloys Schepers1Miriam Hils2Kyra Swiontek3Andrew Flatley4Robert Janowski5Mohammadali Khan Mirzaei6Mohammadali Khan Mirzaei7Michael Dittmar8Neera Chakrapani9Mahesh S. Desai10Mahesh S. Desai11Stefanie Eyerich12Li Deng13Li Deng14Dierk Niessing15Konrad Fischer16Regina Feederle17Simon Blank18Carsten B. Schmidt-Weber19Carsten B. Schmidt-Weber20Christiane Hilger21Tilo Biedermann22Caspar Ohnmacht23Center of Allergy and Environment (ZAUM) and Institute of Allergy Research, Technical University of Munich, School of Medicine, and Helmholtz Center Munich, Research Center for Environmental Health, Neuherberg, GermanyMonoclonal Antibody Core Facility, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyDepartment of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, GermanyDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, LuxembourgMonoclonal Antibody Core Facility, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyInstitute of Structural Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyInstitute of Virology, Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyChair of Prevention of Microbial Diseases, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, GermanyCenter of Allergy and Environment (ZAUM) and Institute of Allergy Research, Technical University of Munich, School of Medicine, and Helmholtz Center Munich, Research Center for Environmental Health, Neuherberg, GermanyDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, LuxembourgDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, LuxembourgOdense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, DenmarkCenter of Allergy and Environment (ZAUM) and Institute of Allergy Research, Technical University of Munich, School of Medicine, and Helmholtz Center Munich, Research Center for Environmental Health, Neuherberg, GermanyInstitute of Virology, Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyChair of Prevention of Microbial Diseases, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, GermanyInstitute of Structural Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyChair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, GermanyMonoclonal Antibody Core Facility, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyCenter of Allergy and Environment (ZAUM) and Institute of Allergy Research, Technical University of Munich, School of Medicine, and Helmholtz Center Munich, Research Center for Environmental Health, Neuherberg, GermanyCenter of Allergy and Environment (ZAUM) and Institute of Allergy Research, Technical University of Munich, School of Medicine, and Helmholtz Center Munich, Research Center for Environmental Health, Neuherberg, Germany0German Center of Lung Research (DZL), Munich, GermanyDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, LuxembourgDepartment of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, GermanyCenter of Allergy and Environment (ZAUM) and Institute of Allergy Research, Technical University of Munich, School of Medicine, and Helmholtz Center Munich, Research Center for Environmental Health, Neuherberg, GermanyThe alpha-Gal epitope (α-Gal) with the determining element galactose-α1,3-galactose can lead to clinically relevant allergic reactions and rejections in xenotransplantation. These immune reactions can develop because humans are devoid of this carbohydrate due to evolutionary loss of the enzyme α1,3-galactosyltransferase (GGTA1). In addition, up to 1% of human IgG antibodies are directed against α-Gal, but the stimulus for the induction of anti-α-Gal antibodies is still unclear. Commensal bacteria have been suggested as a causal factor for this induction as α-Gal binding tools such as lectins were found to stain cultivated bacteria isolated from the intestinal tract. Currently available tools for the detection of the definite α-Gal epitope, however, are cross-reactive, or have limited affinity and, hence, offer restricted possibilities for application. In this study, we describe a novel monoclonal IgG1 antibody (27H8) specific for the α-Gal epitope. The 27H8 antibody was generated by immunization of Ggta1 knockout mice and displays a high affinity towards synthetic and naturally occurring α-Gal in various applications. Using this novel tool, we found that intestinal bacteria reported to be α-Gal positive cannot be stained with 27H8 questioning whether commensal bacteria express the native α-Gal epitope at all.https://www.frontiersin.org/articles/10.3389/fimmu.2022.958952/fullalpha-Galα-GalIgGmonoclonal antibodycarbohydratered meat allergy
spellingShingle Luisa Kreft
Aloys Schepers
Miriam Hils
Kyra Swiontek
Andrew Flatley
Robert Janowski
Mohammadali Khan Mirzaei
Mohammadali Khan Mirzaei
Michael Dittmar
Neera Chakrapani
Mahesh S. Desai
Mahesh S. Desai
Stefanie Eyerich
Li Deng
Li Deng
Dierk Niessing
Konrad Fischer
Regina Feederle
Simon Blank
Carsten B. Schmidt-Weber
Carsten B. Schmidt-Weber
Christiane Hilger
Tilo Biedermann
Caspar Ohnmacht
A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria
Frontiers in Immunology
alpha-Gal
α-Gal
IgG
monoclonal antibody
carbohydrate
red meat allergy
title A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria
title_full A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria
title_fullStr A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria
title_full_unstemmed A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria
title_short A novel monoclonal IgG1 antibody specific for Galactose-alpha-1,3-galactose questions alpha-Gal epitope expression by bacteria
title_sort novel monoclonal igg1 antibody specific for galactose alpha 1 3 galactose questions alpha gal epitope expression by bacteria
topic alpha-Gal
α-Gal
IgG
monoclonal antibody
carbohydrate
red meat allergy
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.958952/full
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