Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice

Toshihisa Nagao, Yoshinori Yamanishi, Kensuke Miyake, Mio Teranishi, Saori Takahashi, Soichiro Yoshikawa, Yohei Kawano, Hajime Karasuyama

Research output: Contribution to journalReview article

Abstract

A hapten is a small molecule that is not immunogenic on its own but can stimulate the production of antibodies at the sensitization phase when conjugated to carrier proteins. The hapten then reacts specifically with the antibodies generated against it to elicit an immune or allergic response at the challenge phase. Here, we compared various carrier proteins conjugated with the same hapten in their ability to induce hapten-specific IgE-mediated allergic responses in vitro and in vivo, and characterized the nature of carrier proteins that determines the magnitude of response at the challenge phase of allergic reactions. Hapten 2,4,6-trinitrophenol (TNP)-conjugated ovalbumin (TNP-OVA) and bovine serum albumin (TNP-BSA) elicited TNP-specific, mast cell-dependent, immediate-type allergic reactions at a comparable level in mice that had been passively sensitized with TNP-specific IgE. In contrast, TNP-OVA but not TNP-BSA efficiently induced a basophil-dependent, IgE-mediated chronic allergic inflammation (IgE-CAI), even though both proteins could stimulate basophils in vitro at a comparable level. By comparing different carrier proteins and structurally modifying them, we found that the formation of large aggregates is crucial for TNP-conjugated carrier proteins to efficiently elicit IgE-CAI, regardless of the type of protein. Thus, the aggregation status of carrier proteins appears to determine the magnitude of allergic response at the challenge phase of hapten-specific IgE-CAI. Our findings suggest that the allergenicity of substances is a matter of importance not only at the sensitization but also at the challenge phase in a certain type of allergy including a basophil-mediated allergic inflammation.

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalInternational Immunology
Volume31
Issue number1
DOIs
Publication statusPublished - Sep 25 2018
Externally publishedYes

Fingerprint

Basophils
Haptens
Carrier Proteins
Hypersensitivity
Immunoglobulin E
Inflammation
Proteins
Ovalbumin
Bovine Serum Albumin
Mast Cells
Antibody Formation
picric acid
Antibodies

Keywords

  • basophil
  • carrier protein
  • hapten
  • IgE
  • protein aggregation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice. / Nagao, Toshihisa; Yamanishi, Yoshinori; Miyake, Kensuke; Teranishi, Mio; Takahashi, Saori; Yoshikawa, Soichiro; Kawano, Yohei; Karasuyama, Hajime.

In: International Immunology, Vol. 31, No. 1, 25.09.2018, p. 41-49.

Research output: Contribution to journalReview article

Nagao, T, Yamanishi, Y, Miyake, K, Teranishi, M, Takahashi, S, Yoshikawa, S, Kawano, Y & Karasuyama, H 2018, 'Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice', International Immunology, vol. 31, no. 1, pp. 41-49. https://doi.org/10.1093/intimm/dxy062
Nagao, Toshihisa ; Yamanishi, Yoshinori ; Miyake, Kensuke ; Teranishi, Mio ; Takahashi, Saori ; Yoshikawa, Soichiro ; Kawano, Yohei ; Karasuyama, Hajime. / Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice. In: International Immunology. 2018 ; Vol. 31, No. 1. pp. 41-49.
@article{514033025dd44681bb4153d8b193fe27,
title = "Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice",
abstract = "A hapten is a small molecule that is not immunogenic on its own but can stimulate the production of antibodies at the sensitization phase when conjugated to carrier proteins. The hapten then reacts specifically with the antibodies generated against it to elicit an immune or allergic response at the challenge phase. Here, we compared various carrier proteins conjugated with the same hapten in their ability to induce hapten-specific IgE-mediated allergic responses in vitro and in vivo, and characterized the nature of carrier proteins that determines the magnitude of response at the challenge phase of allergic reactions. Hapten 2,4,6-trinitrophenol (TNP)-conjugated ovalbumin (TNP-OVA) and bovine serum albumin (TNP-BSA) elicited TNP-specific, mast cell-dependent, immediate-type allergic reactions at a comparable level in mice that had been passively sensitized with TNP-specific IgE. In contrast, TNP-OVA but not TNP-BSA efficiently induced a basophil-dependent, IgE-mediated chronic allergic inflammation (IgE-CAI), even though both proteins could stimulate basophils in vitro at a comparable level. By comparing different carrier proteins and structurally modifying them, we found that the formation of large aggregates is crucial for TNP-conjugated carrier proteins to efficiently elicit IgE-CAI, regardless of the type of protein. Thus, the aggregation status of carrier proteins appears to determine the magnitude of allergic response at the challenge phase of hapten-specific IgE-CAI. Our findings suggest that the allergenicity of substances is a matter of importance not only at the sensitization but also at the challenge phase in a certain type of allergy including a basophil-mediated allergic inflammation.",
keywords = "basophil, carrier protein, hapten, IgE, protein aggregation",
author = "Toshihisa Nagao and Yoshinori Yamanishi and Kensuke Miyake and Mio Teranishi and Saori Takahashi and Soichiro Yoshikawa and Yohei Kawano and Hajime Karasuyama",
year = "2018",
month = "9",
day = "25",
doi = "10.1093/intimm/dxy062",
language = "English",
volume = "31",
pages = "41--49",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice

AU - Nagao, Toshihisa

AU - Yamanishi, Yoshinori

AU - Miyake, Kensuke

AU - Teranishi, Mio

AU - Takahashi, Saori

AU - Yoshikawa, Soichiro

AU - Kawano, Yohei

AU - Karasuyama, Hajime

PY - 2018/9/25

Y1 - 2018/9/25

N2 - A hapten is a small molecule that is not immunogenic on its own but can stimulate the production of antibodies at the sensitization phase when conjugated to carrier proteins. The hapten then reacts specifically with the antibodies generated against it to elicit an immune or allergic response at the challenge phase. Here, we compared various carrier proteins conjugated with the same hapten in their ability to induce hapten-specific IgE-mediated allergic responses in vitro and in vivo, and characterized the nature of carrier proteins that determines the magnitude of response at the challenge phase of allergic reactions. Hapten 2,4,6-trinitrophenol (TNP)-conjugated ovalbumin (TNP-OVA) and bovine serum albumin (TNP-BSA) elicited TNP-specific, mast cell-dependent, immediate-type allergic reactions at a comparable level in mice that had been passively sensitized with TNP-specific IgE. In contrast, TNP-OVA but not TNP-BSA efficiently induced a basophil-dependent, IgE-mediated chronic allergic inflammation (IgE-CAI), even though both proteins could stimulate basophils in vitro at a comparable level. By comparing different carrier proteins and structurally modifying them, we found that the formation of large aggregates is crucial for TNP-conjugated carrier proteins to efficiently elicit IgE-CAI, regardless of the type of protein. Thus, the aggregation status of carrier proteins appears to determine the magnitude of allergic response at the challenge phase of hapten-specific IgE-CAI. Our findings suggest that the allergenicity of substances is a matter of importance not only at the sensitization but also at the challenge phase in a certain type of allergy including a basophil-mediated allergic inflammation.

AB - A hapten is a small molecule that is not immunogenic on its own but can stimulate the production of antibodies at the sensitization phase when conjugated to carrier proteins. The hapten then reacts specifically with the antibodies generated against it to elicit an immune or allergic response at the challenge phase. Here, we compared various carrier proteins conjugated with the same hapten in their ability to induce hapten-specific IgE-mediated allergic responses in vitro and in vivo, and characterized the nature of carrier proteins that determines the magnitude of response at the challenge phase of allergic reactions. Hapten 2,4,6-trinitrophenol (TNP)-conjugated ovalbumin (TNP-OVA) and bovine serum albumin (TNP-BSA) elicited TNP-specific, mast cell-dependent, immediate-type allergic reactions at a comparable level in mice that had been passively sensitized with TNP-specific IgE. In contrast, TNP-OVA but not TNP-BSA efficiently induced a basophil-dependent, IgE-mediated chronic allergic inflammation (IgE-CAI), even though both proteins could stimulate basophils in vitro at a comparable level. By comparing different carrier proteins and structurally modifying them, we found that the formation of large aggregates is crucial for TNP-conjugated carrier proteins to efficiently elicit IgE-CAI, regardless of the type of protein. Thus, the aggregation status of carrier proteins appears to determine the magnitude of allergic response at the challenge phase of hapten-specific IgE-CAI. Our findings suggest that the allergenicity of substances is a matter of importance not only at the sensitization but also at the challenge phase in a certain type of allergy including a basophil-mediated allergic inflammation.

KW - basophil

KW - carrier protein

KW - hapten

KW - IgE

KW - protein aggregation

UR - http://www.scopus.com/inward/record.url?scp=85061127270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061127270&partnerID=8YFLogxK

U2 - 10.1093/intimm/dxy062

DO - 10.1093/intimm/dxy062

M3 - Review article

C2 - 30239735

AN - SCOPUS:85061127270

VL - 31

SP - 41

EP - 49

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 1

ER -