NONREPONSE TO THE HEPATITIS B VACCINE

对乙型肝炎疫苗无反应

• 批准号: 2457783
• 负责人: CHESTER Allan ALPER
• 金额: $ 27.14万
• 依托单位: IMMUNE DISEASE INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2457783
• 关键词: T cell receptor; T lymphocyte; antigen presentation; cytokine; family genetics; hepatitis B; hepatitis B antigens; hepatitis B virus group; hepatitis vaccine; human subject; immune tolerance /unresponsiveness; immunogenetics; major histocompatibility complex; protein biosynthesis; tissue /cell culture

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.

描述（改编自研究者摘要）：乙型肝炎是

项目成果

Circulating CD2+ monocytes are dendritic cells.

• DOI: 10.4049/jimmunol.163.11.5920
• 发表时间: 1999-12
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: K. Crawford;D. Gabuzda;V. Pantazopoulos;J. Xu;C. Clément;E. Reinherz;C. Alper

Hepatitis B surface antigen- and tetanus toxoid-specific clonal expansion of CD4+ cells in vitro determined by TCRBV CDR3 length and nucleotide sequence.

通过 TCRBV CDR3 长度和核苷酸序列确定 CD4 细胞体外乙型肝炎表面抗原和破伤风类毒素特异性克隆扩增。

• DOI: 10.1038/sj.gene.6363729
• 发表时间: 2001
• 期刊: Genes and immunity.
• 作者: Uko,GP;Fraser,PA;Awdeh,ZL;Fici,DA;Crawford,KD;Larsen,CE;Alper,CA
• 通讯作者: Alper,CA