Vance R E, Kraft J R, Altman J D, Jensen P E, Raulet D H
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California Berkeley, Berkeley, California 94720, USA.
J Exp Med. 1998 Nov 16;188(10):1841-8. doi: 10.1084/jem.188.10.1841.
Natural killer (NK) cells preferentially lyse targets that express reduced levels of major histocompatibility complex (MHC) class I proteins. To date, the only known mouse NK receptors for MHC class I belong to the Ly49 family of C-type lectin homodimers. Here, we report the cloning of mouse NKG2A, and demonstrate it forms an additional and distinct class I receptor, a CD94/NKG2A heterodimer. Using soluble tetramers of the nonclassical class I molecule Qa-1(b), we provide direct evidence that CD94/NKG2A recognizes Qa-1(b). We further demonstrate that NK recognition of Qa-1(b) results in the inhibition of target cell lysis. Inhibition appears to depend on the presence of Qdm, a Qa-1(b)-binding peptide derived from the signal sequences of some classical class I molecules. Mouse NKG2A maps adjacent to CD94 in the heart of the NK complex on mouse chromosome six, one of a small cluster of NKG2-like genes. Our findings suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells.
自然杀伤（NK）细胞优先裂解那些主要组织相容性复合体（MHC）I类蛋白表达水平降低的靶细胞。迄今为止，已知的唯一识别MHC I类分子的小鼠NK受体属于C型凝集素同二聚体的Ly49家族。在此，我们报告了小鼠NKG2A的克隆，并证明它形成了另一种独特的I类受体，即CD94/NKG2A异二聚体。使用非经典I类分子Qa-1(b)的可溶性四聚体，我们提供了直接证据表明CD94/NKG2A识别Qa-1(b)。我们进一步证明NK细胞对Qa-1(b)的识别会导致靶细胞裂解的抑制。抑制作用似乎依赖于Qdm的存在，Qdm是一种从某些经典I类分子的信号序列衍生而来的与Qa-1(b)结合的肽段。小鼠NKG2A定位于小鼠6号染色体上NK复合体核心区域中与CD94相邻的位置，是一小簇NKG2样基因之一。我们的研究结果表明，小鼠NK细胞与其人类对应细胞一样，使用多种机制来监测靶细胞上的I类分子表达情况。
