Hanke T, Raulet D H
Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, Germany.
J Immunol. 2001 Mar 1;166(5):3002-7. doi: 10.4049/jimmunol.166.5.3002.
Inhibitory receptors specific for MHC class I molecules are expressed on partially overlapping subpopulations of NK cells and memory T cells. A central question pertinent to NK cell development and function is how the combinatorial expression of different receptors with distinct class I specificities affects functional recognition. We therefore studied the quantitative effects resulting from class I engagement of multiple inhibitory Ly49 receptors. We used a transgenic mouse model in which all NK cells and T cells express two different Ly49 receptors with shared class I specificity. Comparisons of cells from these mice with cells from single transgenic mice and wild-type mice revealed that Ly49 receptors cumulatively inhibit lymphocyte effector functions. Multiple Ly49 interactions also had a cumulative impact on NK cell development. The findings suggest that the interactions of inhibitory receptors with class I are interpreted quantitatively rather than as on/off switches. They have intriguing implications concerning NK cell tolerance and reactivity toward cells with extinguished expression of a limited number of class I molecules.
对MHC I类分子具有特异性的抑制性受体在自然杀伤细胞（NK细胞）和记忆性T细胞部分重叠的亚群上表达。一个与NK细胞发育和功能相关的核心问题是，具有不同I类特异性的不同受体的组合表达如何影响功能识别。因此，我们研究了多个抑制性Ly49受体与I类结合所产生的定量效应。我们使用了一种转基因小鼠模型，其中所有NK细胞和T细胞都表达两种具有共同I类特异性的不同Ly49受体。将这些小鼠的细胞与单转基因小鼠和野生型小鼠的细胞进行比较，结果显示Ly49受体可累积抑制淋巴细胞效应功能。多个Ly49相互作用对NK细胞发育也有累积影响。这些发现表明，抑制性受体与I类的相互作用是通过定量方式来解读的，而不是作为开/关开关。它们对于NK细胞耐受性以及对有限数量I类分子表达缺失的细胞的反应性具有有趣的意义。
