Joost van Neerven R, van t'Hof W, Ringrose J H, Jansen H M, Aalberse R C, Wierenga E A, Kapsenberg M L
Laboratory for Cell Biology and Histology, University of Amsterdam, Academisch Medisch Centrum, The Netherlands.
J Immunol. 1993 Aug 15;151(4):2326-35.
Recent work has indicated the significance of IL-4- and IL-5-secreting allergen-specific human Th2 lymphocytes in the control of immune responses to allergens in atopic individuals. The precise allergenic epitopes that activate these allergen-specific Th2 cells are, however, hardly known. We analyzed the epitope-specificity of T lymphocytes specific for Der p II, one of the major allergens of house dust mite Dermatophagoides pteronyssinus. Using a panel of overlapping synthetic peptides that span the entire Der p II molecule, we could demonstrate that polyclonal Der p II-specific T cell lines prepared from the peripheral blood of five atopic patients can react with at least 10 different epitopes of the molecule. Each donor showed a different pattern of reactivity with the synthetic peptides, suggesting that Der p II contains multiple T cell epitopes that may differ from individual to individual. We studied the specificity of the T cell response to Der p II in more detail in one atopic patient using a short term polyclonal T cell line that strongly reacted to one single peptide (116-129) of the allergen. From this patient we established a panel of 11 Der p II-specific TLC. Ten TLC were of the CD3+ CD4+ phenotype and showed a high IL-4/IFN-gamma production ratio, whereas another TLC expressed CD3 and CD8 and failed to secrete substantial IL-4 and IFN-gamma. The use of at least four different TCR V beta gene segments was shown within this panel TLC. All TLC tested recognized the allergen in an HLA-DR1-restricted manner. Although this patient reacted to only one peptide on the polyclonal level, two T cell epitopes were identified on the clonal level by using synthetic peptides and autologous APC to stimulate the TLC. Combining data of CD4/CD8 expression, TCR V beta usage, and epitope specificity, at least six different types of Der p II-specific TLC could be identified within this patient. Binding of IgE to all synthetic peptides of Der p II is low and of low affinity, which may be of particular importance with respect to possible desensitization protocols using such peptides.
近期研究表明，分泌白细胞介素-4和白细胞介素-5的变应原特异性人Th2淋巴细胞在特应性个体对变应原的免疫反应控制中具有重要意义。然而，激活这些变应原特异性Th2细胞的精确变应原表位却鲜为人知。我们分析了尘螨（Dermatophagoides pteronyssinus）主要变应原之一Der p II特异性T淋巴细胞的表位特异性。使用一组覆盖整个Der p II分子的重叠合成肽，我们能够证明从五名特应性患者外周血制备的多克隆Der p II特异性T细胞系可与该分子的至少10个不同表位发生反应。每个供体对合成肽的反应模式不同，这表明Der p II含有多个可能因人而异的T细胞表位。我们使用对变应原的一个单一肽段（116 - 129）强烈反应的短期多克隆T细胞系，在一名特应性患者中更详细地研究了T细胞对Der p II的反应特异性。从该患者中我们建立了一组11个Der p II特异性TLC。10个TLC为CD3 + CD4 +表型，表现出高IL - 4/IFN -γ产生率，而另一个TLC表达CD3和CD8，且不分泌大量IL - 4和IFN -γ。在该组TLC中显示使用了至少四种不同的TCR Vβ基因片段。所有测试的TLC均以HLA - DR1限制的方式识别变应原。尽管该患者在多克隆水平上仅对一个肽段有反应，但通过使用合成肽和自体抗原呈递细胞刺激TLC，在克隆水平上鉴定出两个T细胞表位。结合CD4/CD8表达、TCR Vβ使用情况和表位特异性的数据，在该患者中可鉴定出至少六种不同类型的Der p II特异性TLC。IgE与Der p II所有合成肽的结合较低且亲和力低，这对于使用此类肽的可能脱敏方案可能特别重要。
