Allergen Ligands in the Initiation of Allergic Sensitization

Thomas, Wayne R.

doi:10.1007/s11882-014-0432-x

Cited by 15 publications

(15 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical and immunological relevance of ligand binding to allergenic proteins has recently been emphasized 12 , 20 , 40 , but mechanisms by which ligands modulate immune-reactivity are not fully understood. In fact, binding of RA had no influence on the IgE binding and cross-linking capacity in sera of children sensitized to milk allergen, being tolerant (MT) or reacting positive to oral cows milk allergen challenge (MA).…”

Section: Discussionmentioning

confidence: 99%

“…The most significant finding, however, was that holo -Bos d 5 impeded any of the investigated immune cell activation. Interestingly, other lipocalin proteins in connection with small hydrophobic ligands have been described to act in a similar manner 40 , 47 . The holo -Bos d 5 mediated effects were thus comparable to the events occurring in the development of natural tolerance to milk and other food allergens 7 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope

Hufnagl

Ghosh

Wagner

et al. 2018

Sci Rep

View full text Add to dashboard Cite

The major cow’s milk allergen Bos d 5 belongs to the lipocalin protein family, with an intramolecular pocket for hydrophobic ligands. We investigated whether Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA), would elicit differential immune responses compared to the unloaded state. By in silico docking an affinity energy of −7.8 kcal/mol was calculated for RA into Bos d 5. Loading of RA to Bos d 5 could be achieved in vitro, as demonstrated by ANS displacement assay, but had no effect on serum IgE binding in tolerant or challenge-positive milk allergic children. Bioinformatic analysis revealed that RA binds to the immunodominant T-cell epitope region of Bos d 5. In accordance, Bos d 5 significantly suppressed the CD3+ CD4+ cell numbers, proliferative response and IL-10, IL-13 and IFN-γ secretion from stimulated human PBMCs only when complexed with RA. This phenomenon was neither associated with apoptosis of T-cells nor with the activation of Foxp3+ T-cells, but correlated likely with enhanced stability to lysosomal digestion due to a predicted overlap of Cathepsin S cleavage sites with the RA binding site. Taken together, proper loading of Bos d 5 with RA may suppress its immunogenicity and prevent its allergenicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope

Hufnagl

Ghosh

Wagner

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The structures of the group 5, 7&21 allergens suggest that they have structures and that can bind lipid, glycoprotein and glycolipids to interact with the innate immune system and affect antigen delivery 2,96 Component resolved diagnosis…”

Section: Biological Activity and Allergenicitymentioning

confidence: 99%

Hierarchy and molecular properties of house dust mite allergens

Thomas

2015

Allergology International

Self Cite

152

141

View full text Add to dashboard Cite

The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24-33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations.

show abstract

“…Lipid ligands carried by allergens, or exposed together, might influence the host response to the specific allergen. Accordingly, immune‐regulatory lipids could significantly contribute to the allergenicity of several proteins . All of these molecules are attractive candidates as non‐self structures recognized by the innate immune system as being capable of inducing Th2‐skewed responses that contribute to allergy in susceptible individuals .…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, immuneregulatory lipids could significantly contribute to the allergenicity of several proteins. 12 All of these molecules are attractive candidates as non-self structures recognized by the innate immune system as being capable of inducing Th2-skewed responses that contribute to allergy in susceptible individuals. 13 Lipids from the pollen coat and furry animals as well as the so-called pollen-associated lipid mediators are codelivered together with the allergens and can modulate the immune responses of predisposed subjects by interacting with the innate immune system and invariant natural killer T (iNKT) cells.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms underlying induction of allergic sensitization by Pru p 3

Tordesillas

Cubells-Baeza

Gómez‐Casado

et al. 2017

Clin Experimental Allergy

View full text Add to dashboard Cite

Background Recently, the nature of the lipid-ligand of Pru p 3, one of the most common plant food allergens in Southern Europe, has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine. However, the origin of its immunological activity is still unknown. Objective We sought to evaluate the role of the Pru p 3 lipid-ligand in the immunogenic activity of Pru p 3. Methods In vitro cultures of different cell types (monocyte-derived dendritic cells (moDCs), PBMCs and epithelial and iNKT-hybridoma cell lines) have been used to determine the immunological capacity of the ligand, by measuring cell proliferation, maturation markers and cytokine production. To study the capacity of the lipid-ligand to promote sensitization to Pru p 3 in vivo, a mouse model of anaphylaxis to peach has been produced and changes in the humoral and basophil responses have been analyzed. Results The lipid-ligand of Pru p 3 induced maturation of moDCsc and proliferation of PBMCs. Its immunological activity resided in the phytosphingosine tail of the ligand. The adjuvant activity of the ligand was also confirmed in vivo, where the complex of Pru p 3-ligand induced higher levels of IgE than Pru p 3 alone. The immunological capacity of the Pru p 3 ligand was mediated by CD1d, as maturation of moDCs was inhibited by anti-CD1d antibodies and Pru p 3-ligand co-localized with CD1d on epithelial cells. Finally, Pru p 3-ligand presented by CD1d was able to interact with iNKTs. Conclusions & Clinical Relevance The Pru p 3 lipid-ligand could act as an adjuvant to promote sensitization to Pru p 3, through its recognition by CD1d receptors. This intrinsic adjuvant activity of the accompanying lipid cargo could be a general essential feature of the mechanism underlying the phenomenon of allergenicity.

show abstract

Allergen Ligands in the Initiation of Allergic Sensitization

Cited by 15 publications

References 113 publications

Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope

Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope

Hierarchy and molecular properties of house dust mite allergens

Mechanisms underlying induction of allergic sensitization by Pru p 3

Contact Info

Product

Resources

About