Higgins J A, Thorpe C J, Hayball J D, O'Hehir R E, Lamb J R
Department of Immunology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, England.
J Allergy Clin Immunol. 1994 May;93(5):891-9. doi: 10.1016/0091-6749(94)90383-2.
The induction of IgE antibodies reactive with the group I allergen of Dermatophagoides species (house dust mite [HDM]), which comprise a major component of the allergic immune response in HDM-atopic individuals, is dependent on the functional activity of specific CD4+ T cells. In this report we demonstrate that for a particular HDM-atopic individual the T-cell response to the group I allergen of Dermatophagoides pteronyssinus (Der p I) is limited to a single region (residues 101-143) of the protein. By mapping the fine antigen specificity with T-cell clones, we observed that the sequence 101-131 of Der p I contains a cluster of at least three overlapping T-cell epitopes. Analysis of the HLA class II restriction specificity of the T-cell clones revealed that the T-cell epitope, residues 110-131, was restricted by HLA-DRB10101. In contrast, peptide Der p I, 110-119 was recognized in association with HLA-DPB10402. However, the ability of cloned T cells to proliferate to the peptide Der p I, 107-119 presented by HLA-DPB10401, HLA-DPB10402, and HLA-DPB1*0501 expressing accessory cells illustrates the heterogeneity of the restriction specificity of this region of Der p I. The application of this information in the design of peptide-based immunotherapy in the management of allergic responses to HDM is discussed.
与尘螨属(屋尘螨[HDM])I组变应原发生反应的IgE抗体的诱导是HDM特应性个体过敏免疫反应的主要组成部分,它依赖于特定CD4 + T细胞的功能活性。在本报告中,我们证明,对于某一特定的HDM特应性个体,其对柏氏禽螨(Der p I)I组变应原的T细胞反应仅限于该蛋白的单个区域(第101 - 143位氨基酸残基)。通过用T细胞克隆绘制精细抗原特异性图谱,我们观察到Der p I的第101 - 131位氨基酸序列包含至少三个重叠的T细胞表位簇。对T细胞克隆的HLA II类限制性特异性分析显示,第110 - 131位氨基酸残基的T细胞表位受HLA - DRB10101限制。相比之下,肽段Der p I 110 - 119与HLA - DPB10402结合时可被识别。然而,克隆的T细胞对表达HLA - DPB10401、HLA - DPB10402和HLA - DPB1*0501的辅助细胞呈递的肽段Der p I 107 - 119发生增殖反应的能力,说明了Der p I该区域限制性特异性的异质性。本文讨论了该信息在设计基于肽段的免疫疗法以治疗对HDM的过敏反应中的应用。