Eiermann T H, Winkelmann S, Ballas M, Wölpl A, Goldmann S F
Department of Transfusion Medicine, University of Ulm, Federal Republic of Germany.
Hum Immunol. 1990 Oct;29(2):117-30. doi: 10.1016/0198-8859(90)90075-z.
This study was undertaken to resolve a positive mixed lymphocyte reaction between HLA-ABC identical, HLA-D different siblings. Three CD3+ CD4+ CD8- alloreactive T-lymphocyte clones, called 2/6, 7/1, and 7/2, were generated and extensively studied. Proliferation of 2/6 cells and 7/2 cells was blocked by anti-DQ monoclonal antibodies (mAbs), whereas anti-DR and DP were not effective. Stimulation of 7/1 cells was inhibited by anti-DR, but not by anti-DQ and DP mAbs. Testing on a well-characterized panel of reference B-lymphoblastoid cell lines showed that the DQ-specific clones 2/6 and 7/2 were able to proliferate upon stimulation by cells carrying the DQw7 and DQw8 but not the DQw9 subtype of DQw3. Clone 7/1 was proliferative towards cells expressing DRw11.1 but not towards DRw11.2- or DRw12-positive cells. Moreover, this clone detected determinants present on some DRw8 cells. Correlation of the reactivity of clone 7/1 with available sequence data suggests that amino acids 67, 71, and 86 of DR beta 1 molecules played a crucial role in forming the epitope recognized by this clone. In contrast, sharing of T-cell epitopes between DQw7 and DQw8 subtypes was not inferable from specific amino acid residues. The implication of these findings for T-cell allorecognition is discussed.
本研究旨在解决 HLA - ABC 相同、HLA - D 不同的同胞之间的阳性混合淋巴细胞反应。生成了三个 CD3 + CD4 + CD8 - 同种异体反应性 T 淋巴细胞克隆,分别称为 2/6、7/1 和 7/2,并对其进行了广泛研究。抗 DQ 单克隆抗体(mAb)可阻断 2/6 细胞和 7/2 细胞的增殖,而抗 DR 和抗 DP 单克隆抗体则无效。抗 DR 可抑制 7/1 细胞的刺激反应,但抗 DQ 和抗 DP 单克隆抗体则无此作用。在一组特征明确的参考 B 淋巴母细胞系上进行测试表明,DQ 特异性克隆 2/6 和 7/2 在受到携带 DQw7 和 DQw8 但不携带 DQw3 的 DQw9 亚型的细胞刺激时能够增殖。克隆 7/1 对表达 DRw11.1 的细胞具有增殖反应,但对 DRw11.2 或 DRw12 阳性细胞则无反应。此外,该克隆还检测到一些 DRw8 细胞上存在的决定簇。克隆 7/1 的反应性与现有序列数据的相关性表明,DRβ1 分子的第 67、71 和 86 位氨基酸在形成该克隆识别的表位中起关键作用。相比之下,无法从特定氨基酸残基推断 DQw7 和 DQw8 亚型之间 T 细胞表位的共享情况。本文讨论了这些发现对 T 细胞同种异体识别的意义。