Prediction of natural killer cell education and repertoire formation by donor immunogenetics

自然杀伤(NK)细胞是免疫系统的一部分，是白细胞，还没有得到广泛的研究。我们还不知道NK细胞是如何发挥作用的，因为控制它们的基因和分子非常复杂，我们仍在建立工具和计算程序来研究这种复杂性。我们的NSERC项目旨在了解基因和分子如何控制NK细胞，使它们在人与人之间发挥不同的功能。我们希望了解NK细胞多样性的程度，以及有限数量的基因如何导致免疫系统功能的如此戏剧性变化。 在这个NSERC项目中，我们将研究与NK细胞功能有关的一小部分基因。对于这些被称为KIR3DL1和人类白细胞抗原B的基因，我们已经有了很好的工具和计算机程序。因此，我们可以用KIR3DL1和人类白细胞抗原B作为起点来理解NK细胞是如何被驱动具有不同的功能的。在我们的第一个目标中，我们将根据NK细胞的已知特征对其进行分类，然后测量使它们或多或少对激活敏感的标记。在我们的下一部分研究中，我们将使用相同类别的NK细胞，并研究该细胞对刺激的反应。我们可以通过用不同的功率触发细胞表面的激活受体，然后测量细胞的反应来做到这一点。 NK细胞的功能因人而异，如果他们被转移到另一个人身上，或者他们暴露在一个新的环境中，这类似于怀孕期间、一个人生病时或他们的免疫系统发育期间发生的事情。通过研究这些变化，我们可以了解NK细胞是如何被编程的。我最近证明，我们可以通过使用一种新的小鼠模型，以类似的方式让NK细胞改变其功能。在这个NSERC项目中，我们现在计划研究控制NK细胞功能的特征，方法是测量它们被新的“环境”改变之前和之后的情况，我们将通过将它们放入这些小鼠来创造它们。 对NK细胞的研究还很少，但它们占人体内白细胞的30%。我们已经知道它们的功能与其他白细胞不同，提出的研究将帮助我们了解基因是如何控制它们独特的功能的。这些实验很重要，因为它们探索了我们不了解的免疫系统的一个特征，引导我们更全面地了解免疫系统是如何工作的。

Natural killer (NK) cells are white blood cells that are part of the immune system, and have not been studied extensively. We do not yet understand how NK cells function because the genes and molecules that control them are very complex, and we are still establishing the tools and computational programs to study this complexity. Our NSERC program aims to understand how genes and molecules control NK cells to make them function differently between people. We are hoping to understand the extent of NK cell diversity, and how a limited number of genes can lead to such dramatic changes in the function of the immune system. In this NSERC project, we will examine small subset of genes that are involved in NK cell function. For these genes, called KIR3DL1 and HLA-B, we already have good tools and computer programs in place. Therefore, we can use KIR3DL1 and HLA-B as a starting point to understand how NK cells are driven to have different functions. In our first aim, we will categorize NK cells based on their known features, then measure the markers that make them more or less sensitive to become activated. In the next part of our studies, we will use the same categories of NK cells, and study how the cell reacts to stimulation. We can do this by triggering the activating receptors on cell surfaces with different amounts of power, then measuring how the cell responds. NK cell function differs between people and changes if they are moved to a different person, or they are exposed to a new environment, which is similar to what happens during pregnancy, when a person becomes sick, or during the development of their immune system. By studying these changes, we can understand how NK cells become programmed. I recently showed that we can make NK cells change their functions in a similar way by using a new mouse model. In this NSERC project, we now plan to study the features that control NK cell function by measuring them before and after they have been changed by the new “environment” that we will create by putting them into these mice. NK cells are highly understudied, but they represent up to 30% of the white blood cells in the human body. We already know that they function differently from other white blood cells, and the studies that propose will help us to understand how genes control their unique function. These experiments are important because they explore a feature of the immune system that we do not understand, guiding us toward a more complete understanding of how the immune system works.