T‐cell epitope‐containing hypoallergenic β‐lactoglobulin for oral immunotherapy in milk allergy

Ueno, Hiroshi M.; Kato, Teruhiko; Ohnishi, Hidenori; Kawamoto, Norio; Kato, Zenichiro; Kaneko, Hideo; Kondo, Naomi; Nakano, Taku

doi:10.1111/pai.12642

T‐cell epitope‐containing hypoallergenic β‐lactoglobulin for oral immunotherapy in milk allergy

Journal Article · Fri Sep 16 00:00:00 EDT 2016 · Pediatric Allergy and Immunology

DOI:https://doi.org/10.1111/pai.12642· OSTI ID:1401467

Ueno, Hiroshi M. ^[1]; Kato, Teruhiko ^[1]; Ohnishi, Hidenori ^[2]; Kawamoto, Norio ^[2]; Kato, Zenichiro ^[2]; Kaneko, Hideo ^[2]; Kondo, Naomi ^[2]; Nakano, Taku ^[1]

Research and Development Department Bean Stalk Snow Co., Ltd. Kawagoe Japan
Department of Pediatrics Graduate School of Medicine Gifu University Gifu Japan

Abstract Background

Optimally hydrolyzed β‐Lactoglobulin (βLg) is a promising milk oral immunotherapy (OIT) candidate with respect to showing reduced B‐cell reactivity but retaining the T‐cell epitope. To demonstrate that an edible hypoallergenic βLg hydrolysate containing the T‐cell epitope is suitable for OIT. We tested how chymotrypsin affected the retention of the T‐cell epitope of βLg when preparing βLg hydrolysates using food‐grade trypsin.

Methods

We investigated the effect of chymotrypsin activity on the formation of the T‐cell epitope‐containing peptide of βLg (βLg _102–124 ) and prepared an edible βLg hydrolysate containing βLg _102–124 using screened food‐grade trypsins. B‐cell reactivity was determined using immunoassays in which ELISA was performed with anti‐βLg rabbit IgG and Western blotting was performed with a milk‐specific IgE antiserum.

Results

In βLg hydrolysis performed by varying the activity of trypsin and chymotrypsin, chymotrypsin activity inhibited the formation of βLg _102–124 with an increase in hydrolysis time in a dose‐dependent manner. βLg _102–124 was generated by two of five food‐grade trypsins used at a ratio of 1:50 (w/w, enzyme/substrate) for 20 h at 40°C. The edible βLg hydrolysate retained βLg _102–124 and showed a reduction in molecular weight distribution and antigenicity against IgG and IgE.

Conclusions

Chymotrypsin activity inhibited the formation of βLg _102–124 in the trypsin hydrolysate of βLg. This βLg trypsin hydrolysate is a novel candidate for peptide‐based OIT in cow's milk allergy for safely inducing desensitization.

View Accepted Manuscript (Publisher)

Sponsoring Organization:: USDOE

OSTI ID:: 1401467

Journal Information:: Pediatric Allergy and Immunology, Journal Name: Pediatric Allergy and Immunology Journal Issue: 8 Vol. 27; ISSN 0905-6157

Publisher:: Wiley-BlackwellCopyright Statement

Country of Publication:: Country unknown/Code not available

Language:: English

References (23)

Effect of Processing on the Allergenicity of Foods Mills, Clare; Johnson, Phil E.; Zuidmeer-Jongejan, Laurian Risk Management for Food Allergy https://doi.org/10.1016/B978-0-12-381988-8.00014-2	book	January 2014
Inhibition of Chymotrypsin Activity in Crystalline Trypsin Preparations Kostka, Vladimir; Carpenter, Frederick H. Journal of Biological Chemistry, Vol. 239, Issue 6 https://doi.org/10.1016/S0021-9258(18)91261-5	journal	June 1964
Interaction of Inactive Derivatives of Chymotrypsin and Trypsin with Protein Inhibitors Feinstein, Gad; Feeney, Robert E. Journal of Biological Chemistry, Vol. 241, Issue 22 https://doi.org/10.1016/S0021-9258(18)96414-8	journal	November 1966
Reduced β-lactoglobulin IgE binding upon in vitro digestion as a result of the interaction of the protein with casein glycomacropeptide Martinez, María J.; Martos, Gustavo; Molina, Elena Food Chemistry, Vol. 192 https://doi.org/10.1016/j.foodchem.2015.07.097	journal	February 2016
Distinctive proteolytic activity of cell envelope proteinase of Lactobacillus helveticus isolated from airag, a traditional Mongolian fermented mare's milk Miyamoto, Mari; Ueno, Hiroshi M.; Watanabe, Masayuki International Journal of Food Microbiology, Vol. 197 https://doi.org/10.1016/j.ijfoodmicro.2014.12.012	journal	March 2015
Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report Burks, A. Wesley; Calderon, Moises A.; Casale, Thomas Journal of Allergy and Clinical Immunology, Vol. 131, Issue 5 https://doi.org/10.1016/j.jaci.2013.01.049	journal	May 2013
Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment Sicherer, Scott H.; Sampson, Hugh A. Journal of Allergy and Clinical Immunology, Vol. 133, Issue 2 https://doi.org/10.1016/j.jaci.2013.11.020	journal	February 2014
State of the art on food allergen immunotherapy: Oral, sublingual, and epicutaneous Jones, Stacie M.; Burks, A. Wesley; Dupont, Christophe Journal of Allergy and Clinical Immunology, Vol. 133, Issue 2 https://doi.org/10.1016/j.jaci.2013.12.1040	journal	February 2014
Microscale affinity purification of trypsin reduces background peptides in matrix-assisted laser desorption/ionization mass spectrometry of protein digests Chamrád, Ivo; Strouhal, Ondřej; Řehulka, Pavel Journal of Proteomics, Vol. 74, Issue 7 https://doi.org/10.1016/j.jprot.2011.02.011	journal	June 2011
Systematic and quantitative comparison of digest efficiency and specificity reveals the impact of trypsin quality on MS-based proteomics Burkhart, Julia Maria; Schumbrutzki, Cornelia; Wortelkamp, Stefanie Journal of Proteomics, Vol. 75, Issue 4 https://doi.org/10.1016/j.jprot.2011.11.016	journal	February 2012
Identification of beta-lactoglobulin-derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy Inoue, R.; Matsushita, S.; Kaneko, H. Clinical Experimental Allergy, Vol. 31, Issue 7 https://doi.org/10.1046/j.1365-2222.2001.01135.x	journal	July 2001
Interaction among human leucocyte antigen-peptide-T cell receptor complexes in cow's milk allergy: the significance of human leucocyte antigen and T cell receptor-complementarity determining region 3 loops Sakaguchi, H.; Inoue, R.; Kaneko, H. Clinical Experimental Allergy, Vol. 32, Issue 5 https://doi.org/10.1046/j.1365-2222.2002.01370.x	journal	May 2002
MIP-1α, MCP-1, and Desensitization in Anaphylaxis from Cow's Milk Glez, Paloma Poza-R.; Franco, Yvelise Barrios-A.; Matheu, Víctor New England Journal of Medicine, Vol. 367, Issue 3 https://doi.org/10.1056/NEJMc1200337	journal	July 2012
The degree of whey hydrolysis does not uniformly affect in vitro basophil and T cell responses of cow's milk-allergic patients Meulenbroek, L. A. P. M.; Oliveira, S.; den Hartog Jager, C. F. Clinical & Experimental Allergy, Vol. 44, Issue 4 https://doi.org/10.1111/cea.12254	journal	March 2014
The response of bovine beta-lactoglobulin-specific T-cell clones to single amino acid substitution of T-cell core epitope Kondo, Masashi; Kaneko, Hideo; Fukao, Toshiyuki Pediatric Allergy and Immunology, Vol. 0, Issue 0 https://doi.org/10.1111/j.1399-3038.2007.00704.x	journal	March 2008
Oral treatment with β-lactoglobulin peptides prevents clinical symptoms in a mouse model for cow's milk allergy Meulenbroek, Laura A. P. M.; van Esch, Betty C. A. M.; Hofman, Gerard A. Pediatric Allergy and Immunology, Vol. 24, Issue 7 https://doi.org/10.1111/pai.12120	journal	September 2013
Lymphocyte Responses to Chymotrypsin- or Trypsin V-Digested β-Lactoglobulin in Patients with Cow's Milk Allergy Kondo, Masashi; Fukao, Toshiyuki; Shinoda, Shinji Allergy, Asthma & Clinical Immunology, Vol. 3, Issue 1 https://doi.org/10.1186/1710-1492-3-1-1	journal	January 2007
Role of specific IgE to β-lactoglobulin in the gastrointestinal phenotype of cow’s milk allergy Poza-Guedes, Paloma; Barrios, Yvelise; González-Pérez, Ruperto Allergy, Asthma & Clinical Immunology, Vol. 12, Issue 1 https://doi.org/10.1186/s13223-016-0111-7	journal	February 2016
Proteolytic Pattern, Antigenicity, and Serum Immunoglobulin E Binding of β-Lactoglobulin Hydrolysates Obtained by Pepsin and High-Pressure Treatments Chicón, R.; López-Fandiño, R.; Alonso, E. Journal of Dairy Science, Vol. 91, Issue 3 https://doi.org/10.3168/jds.2007-0657	journal	March 2008
In vivo methods for testing allergenicity show that high hydrostatic pressure hydrolysates of β-lactoglobulin are immunologically inert López-Expósito, I.; Chicón, R.; Belloque, J. Journal of Dairy Science, Vol. 95, Issue 2 https://doi.org/10.3168/jds.2011-4646	journal	February 2012
Invited Review: β-Lactoglobulin: Binding Properties, Structure, and Function Kontopidis, G.; Holt, C.; Sawyer, L. Journal of Dairy Science, Vol. 87, Issue 4 https://doi.org/10.3168/jds.S0022-0302(04)73222-1	journal	April 2004
Inactivation of Nisin by Alpha-Chymotrypsin Jarvis, B.; Mahoney, R. R. Journal of Dairy Science, Vol. 52, Issue 9 https://doi.org/10.3168/jds.S0022-0302(69)86771-8	journal	September 1969
Hydrolysis under High Hydrostatic Pressure as a Means To Reduce the Binding of β-Lactoglobulin to Immunoglobulin E from Human Sera ChicÓN, R.; Belloque, J.; Alonso, E. Journal of Food Protection, Vol. 71, Issue 7 https://doi.org/10.4315/0362-028X-71.7.1453	journal	July 2008

Similar Records

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy

Journal Article · Mon Jan 16 19:00:00 EST 2023 · Journal of Clinical Investigation · OSTI ID:2423466

Design of an Ara h 2 hypoallergen from conformational epitopes

Journal Article · Sun Dec 31 23:00:00 EST 2023 · Clinical & Experimental Allergy · OSTI ID:2582705

Resistance of structure and antigenic determinations of native hexon of type 1 adenovirus to protease

Journal Article · Mon Feb 09 23:00:00 EST 1987 · Biochemistry (Engl. Transl.); (United States) · OSTI ID:5879218

T‐cell epitope‐containing hypoallergenic β‐lactoglobulin for oral immunotherapy in milk allergy

Citation Formats

References (23)

Similar Records

Related Subjects