免疫原性氨基酸是一类能提高蛋白质免疫原性的非天然氨基酸，如硝基酪氨酸，硝基苯丙氨酸等。近期研究证实：天然蛋白质中插入此类氨基酸能使其突破自身免疫耐受，转化为自身抗原而激活机体免疫系统。很多有价值的肿瘤相关抗原（如：MAGE、gp100、HER-2/neu等）都是自体蛋白，因而存在自身免疫耐受而无法直接用于肿瘤疫苗的开发。免疫原性氨基酸的引入为此类肿瘤疫苗的开发提供了新的思路和方法。本项目拟采用遗传密码扩充技术，将免疫原性氨基酸定点引入到肿瘤相关抗原HER-2/neu中，以期获得能够突破自身免疫耐受的新型肿瘤疫苗。同时比较分析免疫原性氨基酸对HER-2/neu的理化性质、空间结构和免疫原性的影响，深入探讨免疫原性氨基酸在突破自身免疫耐受，形成自身免疫识别机制中的作用，从而为治疗性肿瘤疫苗的开发提供新的理论基础和研究思路。

Immunogenic amino acids is a kind of unnatural amino acids that can improve the immunogenicity of protein, such as nitrotyrosine and nitrobenzene alanine. A recent study confirmed that incorporation of immunogenic amino acids into the protein can break the immunological tolerance of autologous protein. Many valuable vaccine candidate could not be used in clinical for they are autologous proteins, incorporation of immunogenic amino acid into proteins provides a novel method for developing the vaccine from autologous proteins. In this research, we will incorporate immunogenic amino acids into the tumor associated antigen HER-2 by using expanding gene code in order to obtain a novel tumor vaccine. Meanwhile, we will study the effect of immunogenic amino acids on the physicochemical property, structure and immunogenicity of protein. This research will provide a novel method for developing the tumor vaccine.