Human T-cell clones used to define functional epitopes on HLA class II molecules.
Human T-cell clones used to define functional epitopes on HLA class II molecules.
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人类 T 细胞克隆用于定义 HLA II 类分子的功能表位。
DOI：
10.1073/pnas.83.3.762
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发表时间：
1986
影响因子：
11.1
通讯作者：
Fathman,CG
中科院分区：
文献类型：
--
作者：
Weyand,CM;Goronzy,J;Fathman,CG
多克隆试剂已用于在常规血清学和细胞分型中定义 HLA II 类分子。我们生成了人类同种异体反应性 T 细胞克隆来分析 HLA II 类分子的功能精细特异性，这可能对 HLA 和疾病关联现象很重要。我们选择检查 HLA-Dw14，这是一种与幼年类风湿性关节炎相关的 HLA-D 特异性。在本文中，我们提供的数据表明传统的细胞分型不能反映主要组织相容性复合物 II 类分子上 T 细胞表位的分布。我们描述了三个同种异体反应性 T 细胞克隆，它们定义了三个独立的 Dw14 相关 T 细胞表位。其中两个表位位于 DR 区域分子上；第三个位于 DQ 区域产品上。在一组不相关的 DR4 阳性供体中，这三个 DW14 相关决定簇出现频率很高，但彼此之间没有关联。在测试的 DR4 阳性细胞组中，可以看到这三个同种异体决定簇的所有可能的组合排列。三个同种异体决定簇中任何两个的同时表达相当于 Dw14 的阳性分型反应。我们发现 HLA-Dw14 的特征不是独特的同种异体决定簇，而是独立分布的 T 细胞相互作用位点的组合识别，这表明通过使用人类 T 细胞克隆可以更清楚地证明 HLA 和疾病关联的分析。
Polyclonal reagents have been used to define HLA class II molecules in conventional serologic and cellular typing. We generated human alloreactive T-cell clones to analyze the functional fine specificities of HLA class II molecules that might be important for the phenomenon of HLA and disease association. We chose to examine HLA-Dw14, an HLA-D specificity that has been associated with juvenile rheumatoid arthritis. In this paper we have presented data that suggest that conventional cellular typing does not reflect the distribution of T-cell epitopes on major histocompatibility complex class II molecules. We describe three alloreactive T-cell clones that have defined three separate Dw14-associated T-cell epitopes. Two of these epitopes were on a DR-region molecule; the third was located on a DQ-region product. In a panel of unrelated DR4-positive donors, these three DW14-associated determinants were present in a high frequency but were not linked to each other. Within the tested panel of DR4-positive cells, all possible combinatorial arrangements of these three allodeterminants were seen. The concurrent expression of any two of the three allodeterminants was equivalent to a positive typing response for Dw14. Our finding that HLA-Dw14 is not characterized by a unique allodeterminant but by the combinatorial recognition of independently distributed T-cell interaction sites suggests that analysis of HLA and disease association may be more clearly demonstrated through the use of human T-cell clones.