NONREPONSE TO THE HEPATITIS B VACCINE

描述(改编自调查人员摘要)：乙肝 这是世界范围内发病率和死亡率的主要原因。尽管一种疫苗 基于主要的病毒表面蛋白，乙肝表面抗原保护作用最强 在接种疫苗的受试者中，约有4%的人没有反应。 拟议的研究的目的是了解这种机制。 免疫反应和对主要疾病的反应失败 乙肝病毒表面抗原，即乙肝表面抗原。在多大程度上 反应是基因控制的，将通过免疫来定义 同卵双胞胎和他们的直系亲属 与主要组织相容性复合体(MHC)的反应相同 兄弟姐妹。通过对这些家庭和其他家庭的研究以及对 在体外反应中，乙肝表面抗原的主要T细胞表位将是 定义，并且对它们的响应或不响应将与 特定的MHC等位基因和固定的、扩展的单倍型。两国关系 T细胞抗原受体(TCR)Valpha和Vbeta基因与 序列使用和特定的MHC等位基因和扩展单倍型将 在对乙肝表面抗原的应答者和无应答者中进行定义。TCR V基因和 ONT细胞对整个乙肝表面抗原的反应序列也是如此 至于个别表位将与整个曲目进行比较 相同应答者在增强前和无应答者。 其他研究将探索无反应者的缺陷是否存在于 抗原提呈或细胞内功能，包括细胞因子的产生。 调查人员有初步证据表明，他们可以测量出 体外对乙肝表面抗原的初步反应。他们将把这种分析方法应用于 给个人接种疫苗，然后给他们接种疫苗，以确定是否在 体外试验可以预测体内的反应。他们还将使用这种化验方法 确定无反应在多大程度上是由于无反应或 删除反应性T细胞前体。

DESCRIPTION (Adapted from Investigator's abstract): Hepatitis B is a major worldwide cause of morbidity and mortality. Although a vaccine based on the major viral surface protein, HBsAg, protects most immunized subjects, about 4 percent of the population fails to respond. The objective of the proposed research is to understand the mechanisms of the immune response and of the failure of response to the major surface antigen of the hepatitis B virus, HBsAg. The extent to which the response is genetically controlled will be defined by immunizing identical twins and their immediate family members and comparing their response with that of major histocompatibility complex (MHC)- identical siblings. From the study of these and other families and from studies of the response in vitro, the major T-cell epitopes of HBsAg will be defined and the response or nonresponse to them will be correlated with specific MHC alleles and fixed, extended haplotypes. The relationship between T-cell antigen receptor (TCR) Valpha and Vbeta gene and sequence usage and specific MHC alleles and extended haplotypes will be defined in responders and nonresponders to HBsAg. TCR V genes and sequences onT-cells proliferating in response to whole HBsAg as well as to individual epitopes will be compared with the overall repertoire of the same responders before boosting and with that of nonresponders. Other studies will explore whether the defect in nonresponders is in antigen presentation or inT-cell function, including cytokine production. The investigators have preliminary evidence that they can measure a primary response to HBsAg in vitro. They will apply this assay to immunized individuals and then immunize them to determine if the in vitro tests predicts the response in vivo. They will also use the assay to determine the extent to which nonresponse results from anergy or deletion of responsive T-cell precursors.