Wong Kenneth H, Zhou Qian, Prabhu Nayana, Furuhashi Kazuki, Chua Yen Leong, Grotenbreg Gijsbert M, Kemeny David M
Immunology Programme, Life Sciences Institute, Centre for Life Sciences, National University of Singapore, Singapore City, Singapore.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.
Immunology. 2017 Oct;152(2):344-355. doi: 10.1111/imm.12772. Epub 2017 Jul 17.
Blomia tropicalis is the major asthma allergen in the tropics comparable to Dermatophagoides pteronyssinus. However, little is known about the B. tropicalis epitopes recognized by T cells. Our aim was to identify the T-cell epitopes in the major B. tropicalis allergen, Blo t 5, and investigate the potential of the corresponding peptides to inhibit the allergic inflammatory lung response. C57BL/6 mice were immunized with plasmid DNA encoding Blo t 5 and T-cell epitopes identified using the interferon-γ ELISPOT assay with 15-mer overlapping peptides. C57BL/6 mice were sensitized with bone-marrow-derived dendritic cells (BMDC) pulsed with Blo t 5 allergen followed by intranasal Blo t 5 challenge. Two H-2 restricted epitopes (Bt5 and Bt5 ) were recognized by CD4 T cells specific for Blo t 5, but no CD8 epitopes were identified. In mice sensitized with Blo t 5-pulsed BMDC and challenged with intranasal Blo t 5 Bt5 and Bt5 , peptide-specific CD4 T cells were found to secrete the T helper type 2 cytokines interleukin-5 and interleukin-13. Intradermal administration of synthetic peptides encoding the identified T-cell epitopes suppressed allergic airway inflammation to further allergen challenges. Hence, we have identified novel CD4 T-cell epitopes specific for Blo t 5 and demonstrated that these peptides could be employed therapeutically to suppress the T-cell response in a murine model of allergic airway inflammation.
热带无爪螨是热带地区主要的哮喘变应原,与屋尘螨相当。然而,关于T细胞识别的热带无爪螨表位却知之甚少。我们的目的是鉴定热带无爪螨主要变应原Blo t 5中的T细胞表位,并研究相应肽抑制过敏性炎症性肺反应的潜力。用编码Blo t 5的质粒DNA免疫C57BL/6小鼠,并使用15聚体重叠肽通过干扰素-γ ELISPOT试验鉴定T细胞表位。用经Blo t 5变应原脉冲处理的骨髓来源树突状细胞(BMDC)使C57BL/6小鼠致敏,随后进行鼻内Blo t 5激发。对Blo t 5特异的CD4 T细胞识别出两个H-2限制性表位(Bt5和Bt5),但未鉴定出CD8表位。在用经Blo t 5脉冲处理的BMDC致敏并经鼻内Blo t 5 Bt5和Bt5激发的小鼠中,发现肽特异性CD4 T细胞分泌2型辅助性T细胞细胞因子白细胞介素-5和白细胞介素-13。皮内给予编码鉴定出的T细胞表位的合成肽可抑制对进一步变应原激发的过敏性气道炎症。因此,我们鉴定出了对Blo t 5特异的新型CD4 T细胞表位,并证明这些肽可用于治疗性抑制过敏性气道炎症小鼠模型中的T细胞反应。