The non-classical MHC class I molecule Qa-1b inhibits classical MHC class I-restricted cytotoxicity of cytotoxic T lymphocytes
The non-classical MHC class I molecule Qa-1b inhibits classical MHC class I-restricted cytotoxicity of cytotoxic T lymphocytes
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DOI：
10.1093/intimm/13.3.321
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发表时间：
2001-03-01
影响因子：
4.4
通讯作者：
Takei, F
中科院分区：
文献类型：
--
作者：
Lohwasser, S;Kubota, A;Takei, F
CD 94/NKG 2A异二聚体是在小鼠NK细胞亚群上表达的抑制性受体，CD 94/KG 2A识别非经典MHC I类（Ib类）分子Qa-1（B）并抑制NK细胞毒性，Qa-1（B）呈递源自经典MHC 1类分子前导序列的肽。在这里，我们检查了CD 94/NKG 2A在T细胞介导的细胞毒性中的作用，可溶性四聚体Qa-lb与几乎所有CD 8（+）T细胞结合，但不与CD 4（+）T细胞结合。这种结合似乎是由GD 8介导的，因为用GD 8转染的COS细胞也结合Qa-1（B）四聚体。因此，通过单细胞RT-PCR进一步检测T细胞中CD 94/NKG 2的表达。大多数小鼠CD 8（+）T细胞组成性表达CD 94和NKG 2A转录本，而在CD 4（+）T细胞中未检测到。靶细胞上Qa-1（B）和D-k的Go表达显著抑制混合淋巴细胞反应产生的D-k特异性细胞毒性T淋巴细胞的细胞毒性，表明抗原呈递细胞上的Qa-lb与GD 8 T细胞上的CD 94/NKG 2A相互作用并调节经典的MHC I类限制性细胞毒性T细胞。这些结果表明CD 94/NKG 2A作为CD 8（+）T细胞上的抑制性受体具有重要作用。
The CD94/NKG2A heterodimer is an inhibitory receptor expressed on a subset of mouse NK cells, CD94/KG2A recognizes the non-classical MHC class I(class Ib) molecule Qa-1(b) and inhibits NK cytotoxicity, Qa-1(b) presents a peptide derived from the leader sequence of classical MHC class 1 molecules. Here, we examined the role of CD94/NKG2A in T cell-mediated cytotoxicity, Soluble tetrameric Qa-lb bound to almost all CD8(+), but not CD4(+), T cells. This binding seems to be mediated by GD8, because COS cells transfected with GD8 also bound Qa-1(b) tetramer, Therefore, the expression of CD94/NKG2 in T cells was further examined by single-cell RT-PGR. Most murine CD8(+) T cells constitutively expressed CD94 and NKG2A transcripts, whereas they were not detected in CD4(+) T cells, Go-expression of Qa-1(b) and D-k On target cells significantly inhibited cytotoxicity of D-k-specific cytotoxic T lymphocytes generated by mixed lymphocyte reaction, indicating that Qa-lb on antigen-presenting cells interacts with CD94/NKG2A on GD8 T cells and regulates classical MHC class I-restricted cytotoxic T cells. These results suggest a significant role of CD94/NKG2A as an inhibitory receptor on CD8(+) T cells.