NONREPONSE TO THE HEPATITIS B VACCINE

描述（改编自研究者摘要）：B肝炎是 是世界范围内发病率和死亡率的主要原因。虽然疫苗 基于主要的病毒表面蛋白HBsAg， 在接受免疫接种的受试者中，约有4%的人没有反应。 这项研究的目的是了解 免疫反应和免疫失败的主要原因 B型肝炎病毒表面抗原，HBsAg。的程度 免疫反应是由基因控制的， 同卵双胞胎及其直系亲属，并比较他们的 与主要组织相容性复合体（MHC）相同的反应 兄妹从对这些家庭和其他家庭的研究中， 在体外应答中，HBsAg的主要T细胞表位将是 定义和响应或不响应他们将与 特定的MHC等位基因和固定的扩展单倍型。的关系 - T细胞抗原受体（TCR）Valpha和Vbeta基因之间， 序列使用和特定的MHC等位基因和扩展的单倍型将 定义为HBsAg应答者和无应答者。TCR V基因和 T细胞上的序列也响应于整个HBsAg而增殖 将单个表位与总体库进行比较 在加强免疫前相同应答者和无应答者之间。 其他研究将探讨无应答者的缺陷是否与 抗原呈递或T细胞内功能，包括细胞因子产生。 调查人员有初步证据表明，他们可以测量一个 体外对HBsAg的初次应答。他们将把这项试验应用于 免疫个体，然后免疫他们，以确定是否在 体外试验预测体内反应。他们还将使用 以确定无反应性导致无反应的程度， 反应性T细胞前体的缺失。

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.