What is the function of CTLA-4 endocytosis?

免疫反应是一种强大的武器系统，通常针对细菌和病毒等外来入侵者。然而，控制这种武器对于避免对我们自己的身体造成附带伤害至关重要。与所有系统一样，有时会出现故障，人们认为，当免疫系统控制不当时，会出现一些疾病，如类风湿关节炎或胰岛素依赖型糖尿病。这些被称为自身免疫性疾病，当被称为“T细胞”的免疫细胞被不恰当地触发时就会发生。我们正在研究这些细胞的一个主要“关闭开关”，即CTLA-4，它在防止T细胞的附带损伤方面非常重要。然而，CTLA-4类似于一个强大的“开关”，称为CD28，所以按下右键是至关重要的。令人惊讶的是，CTLA-4是在细胞内发现的，而不是像CD28一样在细胞表面，这使得人们很难理解它是如何工作的。一种想法是CTLA-4在需要的时候被送到细胞表面，然而我们的实验表明它不会停留在细胞表面，而是继续回到细胞内部。因此，我们想知道它是否需要在细胞内才能正常工作。本提案中的实验将研究CTLA-4进入细胞的机制以及该过程所需的CTLA-4位。了解这些特性将使我们能够在未来直接测试CTLA-4的内部化对其功能的重要性。

The immune response is a powerful weapons system usually targeted against foreign invaders such as bacteria and viruses. However, control of this weaponary is crucial to avoid collateral damage to our own bodies. As with all systems, faults sometimes occur and it is thought that some diseases such as rheumatoid arthritis or insulin-dependent diabetes, arise when the immune system is not controlled properly. These are known as autoimmune diseases and occur when immune cells, called 'T cells', are triggered inappropriately. We are studying a major 'off switch' on these cells known as CTLA-4, which is extremely important in preventing collateral damage by T cells. However, CTLA-4 is similar to a powerful 'on switch' called CD28 so pressing the right button is critical. Surprisingly CTLA-4 is found inside cells, not on the cell surface like CD28, this makes it difficult to understand how it can work. One idea is that CTLA-4 gets delivered to the cell surface when it's needed, however our experiments show that it doesn't stay at the cell surface but continues to go back inside. We are therefore wondering whether it needs to be inside the cell to work properly. The experiments in this proposal will study the mechanisms used by CTLA-4 to get inside the cell and the bits of CTLA-4 that are needed for this process. Understanding these features will, in the future, allow us to directly test how important internalisation of CTLA-4 is to its function.