Sparholt S H, Larsen J N, Ipsen H, Schou C, van Neerven R J
ALK ABELLO, Hørsholm, Denmark.
Clin Exp Allergy. 1997 Aug;27(8):932-41.
Allergen-specific T lymphocytes play an important role in the pathophysiology of atopic disease. Detailed studies of their epitope-specificity and crossreactivity are required for the development of novel approaches for specific immunotherapy.
The aim of the study was to characterize the fine specificity of Bet v 1-specific T cells from allergic donors.
Polyclonal T-cell lines (TCL) and T-cell clones (TCC), specific for Bet v 1, the major birch (Betula verrucosa) pollen allergen, were isolated from the peripheral blood of three birch-allergic patients. Their epitope-specificity was studied using overlapping synthetic peptides, and crossreactivity with other tree pollen allergens of the Fagales order was evaluated. In addition, the Bet v 1-specific TCC were studied for their phenotype and cytokine production.
All isolated Bet v 1-specific TCC (19/21 CD4+, 2/21 CD8+) reacted with affinity purified Bet v 1, but showed different reactivities with recombinant Bet v 1 (rBet v 1), and with group 1 allergens from other Fagales species. Epitope mapping of rBet v 1-reactive TCC with synthetic peptides of Bet v 1 showed the presence of four T-cell epitopes. Polyclonal T-cell lines reacted with 13 different peptides, and displayed even broader crossreactivity with group 1 pollen allergens from other Fagales members.
This study demonstrates that apart from T-cell epitopes of rBet v 1, many other crossreactive or Bet v 1 isoallergen-specific epitopes exist. This indicates that isoallergenic variation plays an important role in the induction of Bet v 1-specific and crossreactive T-cell responsiveness to allergens.
变应原特异性T淋巴细胞在特应性疾病的病理生理学中起重要作用。开发特异性免疫治疗新方法需要对其表位特异性和交叉反应性进行详细研究。
本研究旨在表征来自过敏供体的Bet v 1特异性T细胞的精细特异性。
从三名桦树过敏患者的外周血中分离出对主要桦树(疣桦)花粉变应原Bet v 1具有特异性的多克隆T细胞系(TCL)和T细胞克隆(TCC)。使用重叠合成肽研究其表位特异性,并评估与壳斗目其他树花粉变应原的交叉反应性。此外,研究了Bet v 1特异性TCC的表型和细胞因子产生情况。
所有分离出的Bet v 1特异性TCC(19/21为CD4 +,2/21为CD8 +)与亲和纯化的Bet v 1反应,但与重组Bet v 1(rBet v 1)以及来自壳斗目其他物种的1类变应原表现出不同的反应性。用Bet v 1的合成肽对rBet v 1反应性TCC进行表位定位显示存在四个T细胞表位。多克隆T细胞系与13种不同的肽反应,并与来自壳斗目其他成员的1类花粉变应原表现出更广泛的交叉反应性。
本研究表明,除了rBet v 1的T细胞表位外,还存在许多其他交叉反应性或Bet v 1同种变应原特异性表位。这表明同种变应原变异在诱导Bet v 1特异性和交叉反应性T细胞对变应原的反应性中起重要作用。