Global Research, ALK-Abelló, Hørsholm, Denmark.
Servicio de Alergia, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
Allergy. 2018 May;73(5):1013-1021. doi: 10.1111/all.13351. Epub 2017 Dec 19.
Profilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as pollen-food syndrome. This study aimed to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins.
The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2 and Mal d 4) were measured in vitro using PBMCs from 26 Spanish grass-allergic donors IgE-sensitized to profilin. Cross-reactivity was addressed in vivo using 2 different mouse strains (BALB/c and C3H).
Phl p 12 and Phl p 1 are released from pollen simultaneously and in similar amounts. Both T-cell response frequency (17/26 donors) and strength were comparable between Phl p 12 and Phl p 1. T-cell cross-reactivity to other profilins correlated with overall sequence homology, and 2 immunodominant epitope regions of Phl p 12 were identified. Data from mice immunized with Phl p 12 showed that cross-reactivity to Bet v 2 was mediated by conserved epitopes and further influenced by additional genetic factors, likely to be MHC II.
The strength, prevalence and cross-reactivity of T-cell responses towards Phl p 12 are comparable to the major allergen Phl p 1, which supports the hypothesis that T cells to Phl p 12 can play an important role in development of allergic symptoms, such as those associated with pollen-food syndrome.
丝状肌球蛋白是主要的泛过敏原，已知其可引起交叉致敏，导致花粉-食物综合征等临床症状。本研究旨在通过测量对临床相关丝状肌球蛋白的流行率、强度和交叉反应性，来确定丝状肌球蛋白致敏患者对 Phl p 12 的 T 细胞反应。
通过质谱和免疫化学测定花粉中 Phl p 过敏原的释放。使用来自 26 名对丝状肌球蛋白过敏的西班牙草过敏供体的 PBMC，体外测量 Phl p 12、Ole e 2、Bet v 2 和 Mal d 4 等丝状肌球蛋白的 T 细胞反应、表位作图和交叉反应性。在体内使用 2 种不同的小鼠品系（BALB/c 和 C3H）来解决交叉反应性问题。
Phl p 12 和 Phl p 1 同时且以相似的量从花粉中释放。Phl p 12 和 Phl p 1 的 T 细胞反应频率（26 名供体中的 17 名）和强度相当。对其他丝状肌球蛋白的 T 细胞交叉反应性与整体序列同源性相关，并且鉴定出 Phl p 12 的 2 个免疫显性表位区域。用 Phl p 12 免疫的小鼠数据表明，Bet v 2 的交叉反应性是由保守表位介导的，并且进一步受到额外遗传因素的影响，可能是 MHC II。
Phl p 12 的 T 细胞反应的强度、流行率和交叉反应性与主要过敏原 Phl p 1 相当，这支持了 Phl p 12 的 T 细胞可能在过敏症状的发展中发挥重要作用的假设，例如与花粉-食物综合征相关的症状。
