Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes.

Autor: Brazhnikov G; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.; Institute for Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Smolnikov E; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia.; Department of Immunology, Institute of Medicine, RUDN University, Moscow, Russia., Litovkina A; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia.; Department of Immunology, Institute of Medicine, RUDN University, Moscow, Russia., Jiang T; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Shatilov A; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Tulaeva I; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.; Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia., Tulaev M; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Karaulov A; Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia., Poroshina A; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Zhernov Y; F. Erismann Institute of Public Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia., Focke-Tejkl M; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.; Karl Landsteiner University of Health Sciences, Krems, Austria., Weber M; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Akinfenwa O; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Elisyutina O; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia.; Department of Immunology, Institute of Medicine, RUDN University, Moscow, Russia., Andreev S; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Shilovskiy I; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Shershakova N; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Smirnov V; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Fedenko E; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Lepeshkova TS; Department of Polyclinic Pediatrics, Ural State Medical University, Yekaterinburg, Russia., Beltyukov EC; Department of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, Yekaterinburg, Russia., Naumova VV; Department of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, Yekaterinburg, Russia., Kundi M; Institute for Hygiene and Applied Immunology, Center for Public Health, Medical University of Vienna, Vienna, Austria., Khaitov M; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia.; Pirogov Russian National Research Medical University, Moscow, Russia., Wiedermann U; Institute for Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Valenta R; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.; National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia.; Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.; Karl Landsteiner University of Health Sciences, Krems, Austria., Campana R; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2023 Dec; Vol. 78 (12), pp. 3136-3153. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1111/all.15865
Abstrakt: Background: The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail.
Objective: To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation.
Methods: Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG 1 and IgG 4 reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis. The ability of Bet v 1-specific serum antibodies from non-allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1-derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non-allergic subjects to modulate Bet v 1-induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients.
Results: IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG 1 and IgG 4 antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen-containing food. Natural Bet v 1-specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1-specific basophil activation.
Conclusion: IgE and IgG antibodies from BPA patients and birch pollen-exposed non-sensitized subjects recognize different epitopes. These findings explain why natural allergen-specific IgG do not protect against allergic symptoms and suggest that allergen-specific IgE and IgG have different clonal origin.
(© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE