Lipid Ligands and Allergenic LTPs: Redefining the Paradigm of the Protein-Centered Vision in Allergy

Abstract

Lipid Transfer Proteins (LTPs) have been described as one of the most prevalent and cross-reactive allergen families in the general population. They are widely distributed among the plant kingdom, as well as in different plant organs ranging from pollen to fruits. Thus, they can initiate allergic reactions with very different outcomes, such as asthma and food allergy. Several mouse models have been developed to unravel the mechanisms that lead LTPs to promote such strong sensitization patterns. Interestingly, the union of certain ligands can strengthen the allergenic capacity of LTPs, suggesting that not only is the protein relevant in the sensitization process, but also the ligands that LTPs carry in their cavity. In fact, different LTPs with pro-allergenic capacity have been shown to transport similar ligands, thus positioning lipids in a central role during the first stages of the allergic response. Here, we offer the latest advances in the use of experimental animals to study the topic, remarking differences among them and providing future researchers a tool to choose the most suitable model to achieve their goals. Also, recent results derived from metabolomic studies in humans are included, highlighting how allergic diseases alter the lipidic metabolism toward a pathogenic state in the individual. Altogether, this review offers a comprehensive body of work that sums up the background evidence supporting the role of lipids as modulators of allergic diseases. Studying the role of lipids during allergic sensitization might broaden our understanding of the molecular events leading to tolerance breakdown in the epithelium, thus helping us to understand how allergy is initiated and established in the individuals.

Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines

“…Their folded structure presents four disulphide bridges that confers the protein high thermal stability and pH resistance, being able to maintain its functionality at high temperatures and extreme pH (both basic and acid) ( 28 , 39 ). Pru p 3 is the major allergen from peach ( 41 ). However, patients sensitized to it can also develop allergic reactions when consuming other fruits from the Rosaceae family, especially apple, apricot and plum ( 42 ).…”

“…For this reason, measurement of sIgE levels in sera constitutes a routine method commonly used by physicians to diagnose LTP allergy ( 27 ). In addition, other immunoglobulin subtypes, such as sIgG1 and sIgG2a, can also be usually identified in murine models of the disease ( 41 ).…”

IgE epitopes of Ara h 9, Jug r 3, and Pru p 3 in peanut-allergic individuals from Spain and the US

“…These epitopes are further conserved in Ara h 9 and Jug r 3. As LTPs are highly similar and homologous to one another, it is expected that some similarity would be expected among IgE epitopes, which explains the high levels of cross reactivity seen among LTPs from various plant sources ( 40 , 45 ). One can presume that the epitopes found in our study are likely the accurate epitopes for this allergen; however, further experimentation is required to confirm the specific residues required for IgE binding to Ara h 9 and homologs in different geographical locations.…”

Plant lipid transfer proteins' ligand enhances allergic sensitization to non‐related proteins in murine models

“…Jaime Tome-Amat 1,2 Zulema Gonzalez-Klein 1,2 Diego Pazos-Castro 1,2 Jose Luis Resuela-Gonzalez 1,2 Gonzalo Vilchez-Pinto 1,2 Helena Berreiros-Hortala 1 Lucia Palacio-Garcia 3 Sergio Fernandez-Bravo 3…”

“…In this context, protein ligands have gained attention since the ligand carried by some plant pathogenesis-related proteins (PRs) are implicated in allergic sensitization. 1,2 Plant lipid transfer proteins (Plant-LTPs), main food allergens, transport a specific lipid ligand (LTPs' ligand) consisting of a polar head derived from camptothecin, linked through an amide bond to aThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.…”