T Cell Epitope Peptide Therapy for Allergic Diseases.
T Cell Epitope Peptide Therapy for Allergic Diseases.
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DOI：
10.1007/s11882-015-0587-0
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发表时间：
2016-02
影响因子：
5.5
通讯作者：
Rolland JM
中科院分区：
文献类型：
--
作者：
O'Hehir RE;Prickett SR;Rolland JM
仔细选择主要过敏原的显性 T 细胞表位肽，这些肽显示出与多种 MHC II 类分子结合的简并性，可以在精细的治疗策略中诱导对过敏原的临床和免疫耐受。从体外研究产生的肽诱导 T 细胞无反应性的最初概念出发，概念验证小鼠模型和蓬勃发展的人体试验随之而来。目前对 T 细胞反应性短过敏原肽或长连续重叠肽混合物进行的随机、双盲、安慰剂对照临床试验令人鼓舞，皮内给药至非发炎皮肤是首选给药方式。确切的免疫学机制尚未解决，但特异性无反应、Th2 细胞缺失、免疫偏差和 Treg 诱导似乎与此有关。一系列气源性过敏原疗法（猫、屋尘螨、草花粉）的显着疗效（特别是短期治疗）以及无关紧要的非系统性不良事件可能预示着一种新的过敏疗法，即合成肽免疫调节表位（SPIRE）。
Careful selection of dominant T cell epitope peptides of major allergens that display degeneracy for binding to a wide array of MHC class II molecules allows induction of clinical and immunological tolerance to allergen in a refined treatment strategy. From the original concept of peptide-induced T cell anergy arising from in vitro studies, proof-of-concept murine models and flourishing human trials followed. Current randomized, double-blind, placebo-controlled clinical trials of mixtures of T cell-reactive short allergen peptides or long contiguous overlapping peptides are encouraging with intradermal administration into non-inflamed skin a preferred delivery. Definitive immunological mechanisms are yet to be resolved but specific anergy, Th2 cell deletion, immune deviation, and Treg induction seem implicated. Significant efficacy, particularly with short treatment courses, in a range of aeroallergen therapies (cat, house dust mite, grass pollen) with inconsequential non-systemic adverse events likely heralds a new class of therapeutic for allergy, Synthetic Peptide Immuno-Regulatory Epitopes (SPIRE).