IMPORTANCE OF HLA-DQ AND HLA-DP RESTRICTION ELEMENTS IN T-CELL RESPONSES TO SOLUBLE-ANTIGENS - MUTATIONAL ANALYSIS
IMPORTANCE OF HLA-DQ AND HLA-DP RESTRICTION ELEMENTS IN T-CELL RESPONSES TO SOLUBLE-ANTIGENS - MUTATIONAL ANALYSIS
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DOI：
10.1016/0198-8859(87)90086-3
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发表时间：
1987-03-01
期刊：
影响因子：
2.7
通讯作者：
PIOUS, D
中科院分区：
文献类型：
--
作者：
MELLINS, E;WOELFEL, M;PIOUS, D
我们描述了一种新的方法来描绘抗原特异性的人类T细胞系引起的限制性元件。EBV转化的B细胞系和同源HLA II类抗原缺失突变体用于将可溶性抗原呈递给免疫T细胞。以这种方式，有可能评估单个II类基因座对T细胞的限制性库的独立贡献。与其他方法的限制性元件分析得到的结果相比，我们发现，约40%的T细胞反应在几种抗原是由非DR II类分子的限制。突变分析和阻断II类特异性单克隆抗体表明，非DR限制性反应来自DQ和DP编码的决定簇。我们还发现特定的DR/DQ单倍型偏好的一些，但不是所有的抗原的介绍。使用一个突变体，只表达的DQ 1分子，是来自DR 1，DQ 1的亲本系，我们证明了一个功能分裂的血清学定义的DQ 1分子一致的电泳变异之间的DQ 1分子连接到DR 1和那些连接到DR 2。一个单一的II类蛋白质的表达不同的突变体对揭示了一个更广泛的使用可用的II类限制性元件比以前认识到的。
We describe a new approach to delineating the restriction elements caused by antigen-specific human T-cell lines. EBV-transformed B cell lines and congenic HLA class II antigen-loss mutants are used to present soluble antigen to immune T cells. In this way it is possible to assess the independent contribution of individual class II loci to the restriction repertoire of the T cells. In contrast to results obtained with other methods of restriction element analysis, we find that approximately 40% of the T-cell response in several antigens is restricted by non-DR class II molecules. Both mutational analysis and blocking by class II specific monoclonal antibodies demonstrate that the non-DR restricted responses derive from DQ and DP-encoded determinants. We also find specific DR/DQ haplotype preferences for the presentation of some but not all antigens. Using a mutant that expresses only the DQ1 molecule, and is derived from a DR1, DQ1 parent line, we demonstrate a functional split of serologically defined DQ1 molecules consistent with the electrophoretic variation reported between DQ1 molecules linked to DR1 and those linked to DR2. Pairs of mutants that differ by expression of a single class II protein reveal a much broader use of available class II restriction elements than previously recognized.