Grass-specific CD4+T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy
Grass-specific CD4+T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy
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DOI：
10.1111/cea.12324
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发表时间：
2014-07-01
影响因子：
6.1
通讯作者：
Kwok, W. W.
中科院分区：
文献类型：
--
作者：
Archila, L. D.;DeLong, J. H.;Kwok, W. W.
从概念上讲，过敏反应可能涉及抗体或T细胞的交叉反应性。虽然已经观察到草花粉过敏原之间的IgE交叉反应性，但在过敏原特异性T细胞水平上的交叉反应性较少被记录。交叉反应模式的识别可以提高我们的理解，从而优化更好的免疫治疗策略。目的以草地蝗虫为模型，研究DR 04：01限制性T细胞表位在变应原特异性CD 4 + T细胞水平的交叉反应性。方法体外培养具有早熟禾科植物特异性抗原表位的花粉过敏受试者的血液单核细胞后，用APC标记的DR 04：01/草红四聚体和PE标记的DR 04：01/早熟禾科植物同源四聚体进行双重四聚体染色，以鉴定6名受试者中变应原特异性DR 04：01限制性T细胞之间的交叉反应性。直接离体染色使得能够比较不同的早熟禾科草花粉反应性T细胞的频率和表型。细胞内细胞因子染色（ICS）测定也用于检查这些T细胞的表型。结果可检测到不同程度交叉反应的T细胞。Poa p 197 -116、Lol p 1221 -240、Lol p 5a 199-218和Poa p 5a 199-218被鉴定为最低交叉反应性T细胞表位，其不显示与Phl p 1和Phl p 5a表位的交叉反应性。离体四聚体染色测定证明识别这些最低交叉反应性T细胞表位的T细胞存在于草花粉过敏受试者中。结论并非所有具有序列同源性的早熟禾科禾属植物表位都具有交叉反应性。具有与Phlp特异性T细胞相当的频率、表型和功能性的非交叉反应性T细胞表明，对于免疫疗法，应考虑多变应原系统而不是单变应原系统。
Background Conceptually, allergic responses may involve cross-reactivity by antibodies or T-cells. While IgE cross-reactivity among grass-pollen allergens has been observed, cross-reactivity at the allergen-specific T-cell level has been less documented. Identification of the patterns of cross-reactivity may improve our understanding, allowing optimization of better immunotherapy strategies. Objectives We use Phleum pratense as model for the studying of cross-reactivity at the allergen-specific CD4+ T cell level among DR04:01 restricted Pooideae grass-pollen T-cell epitopes. Methods After in vitro culture of blood mono-nucleated cells from grass-pollen-allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC-labelled DR04:01/Phleum pratense tetramers and PE-labelled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross-reactivity among allergen-specific DR04:01-restricted T-cells in six subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass-pollen reactive T-cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T-cells. Results T-cells with various degrees of cross-reactive profiles could be detected. Poa p 1 97-116, Lol p 1 221-240, Lol p 5a 199-218, and Poa p 5a 199-218 were identified as minimally cross-reactive T-cell epitopes that do not show cross-reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T-cells that recognized these minimally cross-reactive T-cell epitopes are present in Grass-pollen-allergic subjects. Conclusions Our results suggest that not all Pooideae grass epitopes with sequence homology are cross-reactive. Non-cross-reactive T-cells with comparable frequency, phenotype and functionality to Phl p-specific T-cells suggest that a multiple allergen system should be considered for immunotherapy instead of a mono-allergen system.