B7-H3和B7-H4是重要的共刺激分子，在免疫应答和调节中起着极为重要的作用，但至今其受体尚未克隆，以致阻碍了生物学功能的研究。我们前期研究发现，B7家族的不同分子在生物中有着不同的进化顺序，其受体的进化与它们的进化历史极为相近，受体与配体之间存在着共进化；同时也证实了斑马鱼中B7.1、B7.2分子和受体CD28、CTLA-4的共表达，以及B7-H3、B7-H4分子在斑马鱼中的表达。本项目旨在以同源比对和共进化分析为主线，以斑马鱼作为研究对象，采用同源序列分析、结构模拟等计算手段，以及real time PCR、基因组修饰技术CRISPR-Cas9等实验方法，搜索斑马鱼基因组找到可能的B7-H3和B7-H4的未知受体，并进一步进行实验验证和功能分析。本研究将从同源比对和共进化分析这一新的视角寻找B7-H3和B7-H4受体，为共刺激分子作用的机理机制研究提供新的策略。

B7-H3 and B7-H4 are important costimulatory molecules, which play important roles in immune response and regulation, while their receptors remain unknown and the unknown receptors blocked the study of their biological functions. Our previous studies have found that different molecules of B7 family in different species experienced different evolution paths, the receptors and ligands experienced similar evolution history, and have proved the co-expressed of B7.1/2 and their receptors CD28/CTLA-4 in Danio Rerio, and proved the expression of B7-H3/B7-H4 in Danio Rerio. This project aims to use homologous comparison and co-evolution methods to search possible receptors in Danio Rerio genome for B7-H3 and B7-H4, and use real time PCR and CRISPR-Cas9 methods to perform experimental verification and function analysis. This project uses new methods to search for receptors of B7-H3 and B7-H4, and provides new strategies for understanding of molecular mechanism of costimulatory molecules.