A single amino acid substitution in the alpha 3 domain of an H-2 class I molecule abrogates reactivity with CTL.
A single amino acid substitution in the alpha 3 domain of an H-2 class I molecule abrogates reactivity with CTL.
复制标题
DOI：
10.1084/jem.166.4.956
复制
发表时间：
1987-10-01
期刊：
影响因子：
--
通讯作者：
Rajan TV
中科院分区：
文献类型：
--
作者：
Potter TA;Bluestone JA;Rajan TV
我们之前描述了一个体细胞，表达一个变异的H-2DD分子，而不是同种异体反应的抗DD CTL的靶点。突变的细胞系由于未能表达存在于H-2DDα3区域的血清学表位而被分离。在本研究中，对该体细胞变异体的DD分子的α3结构域进行了测序，并鉴定了导致227位谷氨酸到赖氨酸替换的单核苷酸变化。这种改变通过寡核苷酸定向突变在克隆的H-2DD基因中重现。转染该突变基因的细胞不被抗H-2DD CTL杀伤。由于以前使用杂交H-2 I类分子的研究已经证实，α3结构域不表达CTL识别的等位基因特异性决定簇，所以我们的结果提出了H-2 I类分子α3结构域中的残基对CTL识别至关重要并构成CTL识别的保守(或单态)决定簇的可能性。
We previously described a somatic cell expressing a variant H-2Dd molecule that did not serve as a target for alloreactive anti-Dd CTL. The mutant cell line had been isolated by its failure to express a serological epitope present on the H-2Dd alpha 3 domain. In the present study the alpha 3 domain of the Dd molecule of this somatic cell variant was sequenced and a single nucleotide change resulting in a glutamic acid to lysine substitution at residue 227 was identified. This change was reproduced in the cloned H-2Dd gene by oligonucleotide- directed mutagenesis. Cells transfected with this mutant gene were not killed by anti-H-2Dd CTL. Because previous studies using hybrid H-2 class I molecules had established that the alpha 3 domain does not express allele-specific determinants recognized by CTL, our results raise the possibility that residues in the alpha 3 domain of H-2 class I molecules are critical for CTL recognition and constitute a conserved (or monomorphic) determinant recognized by CTL.