O'Hehir Robyn E, Prickett Sara R, Rolland Jennifer M
Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Commercial Road, Melbourne, Victoria, 3004, Australia.
Department of Immunology, Monash University, Melbourne, Victoria, Australia.
Curr Allergy Asthma Rep. 2016 Feb;16(2):14. doi: 10.1007/s11882-015-0587-0.
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).
精心挑选主要过敏原的显性T细胞表位肽，这些肽与多种II类主要组织相容性复合体（MHC）分子结合时具有简并性，这使得在一种精细的治疗策略中能够诱导对过敏原的临床和免疫耐受。从体外研究中产生的肽诱导T细胞无反应性的最初概念开始，随后出现了概念验证小鼠模型和蓬勃发展的人体试验。目前，关于T细胞反应性短过敏原肽或长连续重叠肽混合物的随机、双盲、安慰剂对照临床试验令人鼓舞，皮内注射到未发炎皮肤是首选的给药方式。确切的免疫机制尚待解决，但特异性无反应性、Th2细胞缺失、免疫偏离和调节性T细胞诱导似乎与之相关。在一系列气传过敏原疗法（猫、屋尘螨、草花粉）中，尤其是短疗程治疗时，具有显著疗效，且非全身性不良事件无关紧要，这可能预示着一类新的过敏治疗方法——合成肽免疫调节表位（SPIRE）的出现。
