Identification of a highly promiscuous and an HLA allele‐specific T‐cell epitope in the birch major allergen Bet v 1: HLA restriction, epitope mapping and TCR sequence comparisons

Friedl‐Hajek,; Spangfort,; Schou,; Breiteneder,; Yssel,; Neerven, R. J. Joost van

doi:10.1046/j.1365-2222.1999.00489.x

Cited by 23 publications

(18 citation statements)

References 37 publications

(81 reference statements)

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“…Some of the known Bet v 1a T cell epitopes contain tyrosine residues [24,25,26,27], but it is unknown if these tyrosines might become nitrated. Tyrosine nitration in proteins is selective, since some tyrosine residues are highly susceptible for nitration whereas others cannot be nitrated at all [10].…”

Section: Discussionmentioning

confidence: 99%

Nitration Enhances the Allergenic Potential of Proteins

Gruijthuijsen

Grieshuber²,

Stöcklinger³

et al. 2006

Int Arch Allergy Immunol

117

113

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Background: Recent investigations have shown that proteins, including Bet v 1a, are nitrated by exposure to polluted urban air. We have investigated immunogenic and allergenic properties of in vitro nitrated allergens in in vivo models. Methods: Untreated and nitrated samples of ovalbumin or Bet v 1a were compared for their ability to stimulate proliferation and cytokine secretion in splenocytes from DO11.10 or from sensitized BALB/c mice, and for their ability to induce specific immunoglobulin (Ig)G1, IgG2a and IgE in sensitized mice. Additionally, sera from birch pollen-allergic individuals were analysed for IgE and IgG specific for nitrated Bet v 1a. Results: Upon splenocyte stimulation with nitrated as compared with unmodified allergens, proliferation as well as interleukin 5 and interferon-γ production were enhanced. Sera of mice sensitized with nitrated allergens showed elevated levels of specific IgE, IgG1 and IgG2a, compared with sera from mice sensitized with unmodified allergens. Moreover, cross-reactivity of antibodies against unrelated, nitrated allergens was observed in mice. We also found higher amounts of functional, specific IgE against nitrated than against untreated Bet v 1a in sera from birch pollen-allergic patients. Conclusions: Our findings suggest that nitration enhances allergic responses, which may contribute to an increased prevalence of allergic diseases in polluted urban environments.

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Section: Discussionmentioning

confidence: 99%

Nitration Enhances the Allergenic Potential of Proteins

Gruijthuijsen

Grieshuber²,

Stöcklinger³

et al. 2006

Int Arch Allergy Immunol

117

113

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“…However, peptide affinity for the class II MHC protein is a poor predictor of epitope dominance in influenza virus hemagglutinin (HA) (22) and other antigens (40,46,52). The weak influence of MHC-peptide affinity on epitope dominance is further indicated by the frequent observation of "promiscuous" or "universal" CD4 ϩ epitopes, which are dominant in multiple MHC backgrounds (17,20,28,39,50,54,60). Thus, other factors exert a major influence on epitope immunogenicity.…”

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confidence: 99%

Three-Dimensional Structure Determines the Pattern of CD4⁺T-Cell Epitope Dominance in Influenza Virus Hemagglutinin

Landry

2008

J Virol

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The structural context of a CD4؉ T-cell epitope is known to influence immunodominance at the level of antigen processing, but general rules have not emerged. Dominant epitopes of influenza virus hemagglutinin are found to be localized to the C-terminal flanks of conformationally stable segments identified by low crystallographic B-factors or high COREX residue stabilities. The bias toward C-terminal flanks is distinctive for antigens from the influenza virus. Dominant epitopes in antigens/allergens from other sources also localize to the flanks of stable segments but are found on either N-or C-terminal flanks. Thus, dominance arises from preferential endoproteolytic nicking between stable segments followed by loading of fragment terminal regions into antigen-presenting proteins. This mechanism probably arose in order to direct CD4 ؉ responses onto sequences that are conserved for structure and function. Structure-guided presentation could enhance protection against genetically drifting influenza virus variants but most likely reduces protection against new viral subtypes.

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“…Based on these early observations, therefore, it appears that a relatively small number of carefully selected peptides from an allergen may be efficacious in the treatment of allergic disease. Interestingly, similarly promiscuous peptides have been identified in other allergens such as Bet v 1 [18]and bee venom phospholipase A 2 [19]. …”

Section: Materials Methods and Resultsmentioning

confidence: 99%

Mechanisms of T Cell Peptide Epitope-Dependent Late Asthmatic Reactions

Larché

Haselden²,

Oldfield³

et al. 2001

Int Arch Allergy Immunol

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Short peptide sequences corresponding to T cell epitopes have been identified in the major cat allergen Fel d 1. In order to directly activate allergen-specific T cells in cat-allergic asthmatic individuals, peptides were administered by intradermal injection. Subsequently, a proportion of subjects experienced a delayed reduction of airway calibre manifested as a decrease in FEV₁. Changes in lung function occurred approximately 3 h after peptide injection, peaked at 6 h and resembled an isolated late asthmatic reaction (LAR). Using molecular tissue typing techniques, it was determined that many of the individuals experiencing isolated LAR expressed particular HLA-DR molecules. These molecules were shown in subsequent experiments to bind individual peptides within the preparation and thus to activate T cells in a major histocompatibility complex (MHC)-restricted fashion. The precise mechanisms whereby MHC-restricted activation of allergen-specific T cells gives rise to bronchoconstriction are currently under investigation.

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Identification of a highly promiscuous and an HLA allele‐specific T‐cell epitope in the birch major allergen Bet v 1: HLA restriction, epitope mapping and TCR sequence comparisons

Cited by 23 publications

References 37 publications

Nitration Enhances the Allergenic Potential of Proteins

Nitration Enhances the Allergenic Potential of Proteins

Three-Dimensional Structure Determines the Pattern of CD4⁺T-Cell Epitope Dominance in Influenza Virus Hemagglutinin

Mechanisms of T Cell Peptide Epitope-Dependent Late Asthmatic Reactions

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Identification of a highly promiscuous and an HLA allele‐specific T‐cell epitope in the birch major allergen Bet v 1: HLA restriction, epitope mapping and TCR sequence comparisons

Cited by 23 publications

References 37 publications

Nitration Enhances the Allergenic Potential of Proteins

Nitration Enhances the Allergenic Potential of Proteins

Three-Dimensional Structure Determines the Pattern of CD4+T-Cell Epitope Dominance in Influenza Virus Hemagglutinin

Mechanisms of T Cell Peptide Epitope-Dependent Late Asthmatic Reactions

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Three-Dimensional Structure Determines the Pattern of CD4⁺T-Cell Epitope Dominance in Influenza Virus Hemagglutinin