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在对丝氨酸蛋白酶抑制剂过敏的西班牙患者中,对次要过敏原 Phl p 12 存在强烈而频繁的 T 细胞反应。

Strong and frequent T-cell responses to the minor allergen Phl p 12 in Spanish patients IgE-sensitized to Profilins.

机构信息

Global Research, ALK-Abelló, Hørsholm, Denmark.

Servicio de Alergia, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.

出版信息

Allergy. 2018 May;73(5):1013-1021. doi: 10.1111/all.13351. Epub 2017 Dec 19.

Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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