Lohwasser S, Kubota A, Salcedo M, Lian R H, Takei F
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3 Canada.
Int Immunol. 2001 Mar;13(3):321-7. doi: 10.1093/intimm/13.3.321.
The CD94/NKG2A heterodimer is an inhibitory receptor expressed on a subset of mouse NK cells. CD94/NKG2A 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 I molecules. Here, we examined the role of CD94/NKG2A in T cell-mediated cytotoxicity. Soluble tetrameric Qa-1(b) bound to almost all CD8(+), but not CD4(+), T cells. This binding seems to be mediated by CD8, because COS cells transfected with CD8 also bound Qa-1(b) tetramer. Therefore, the expression of CD94/NKG2 in T cells was further examined by single-cell RT-PCR. Most murine CD8(+) T cells constitutively expressed CD94 and NKG2A transcripts, whereas they were not detected in CD4(+) T cells. Co-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-1(b) on antigen-presenting cells interacts with CD94/NKG2A on CD8 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.
CD94/NKG2A异二聚体是一种在小鼠自然杀伤（NK）细胞亚群上表达的抑制性受体。CD94/NKG2A识别非经典的MHC I类（Ib类）分子Qa-1(b)，并抑制NK细胞的细胞毒性。Qa-1(b)呈递源自经典MHC I类分子前导序列的肽段。在此，我们研究了CD94/NKG2A在T细胞介导的细胞毒性中的作用。可溶性四聚体Qa-1(b)与几乎所有CD8(+) T细胞结合，但不与CD4(+) T细胞结合。这种结合似乎是由CD8介导的，因为转染了CD8的COS细胞也能结合Qa-1(b)四聚体。因此，通过单细胞逆转录聚合酶链反应（RT-PCR）进一步检测了T细胞中CD94/NKG2的表达。大多数小鼠CD8(+) T细胞组成性表达CD94和NKG2A转录本，而在CD4(+) T细胞中未检测到。靶细胞上Qa-1(b)和D(k)的共表达显著抑制了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-1(b)与CD8 T细胞上的CD94/NKG2A相互作用，并调节经典MHC I类限制性细胞毒性T细胞。这些结果表明CD94/NKG2A作为CD8(+) T细胞上的抑制性受体具有重要作用。
