REGULATION OF TAP-1 AND MHC-I IN RESPIRATORY PAPILLOMAS

TAP-1 和 MHC-I 在呼吸道乳头状瘤中的调节

• 批准号: 6379184
• 负责人: Andrea Vambutas
• 金额: $ 12.1万
• 依托单位: LONG ISLAND JEWISH MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379184
• 关键词: MHC class I antigen; calcium binding protein; fluorescence microscopy; gene expression; genetic regulation; human papillomavirus; human tissue; immediate early protein; immunocytochemistry; immunoprecipitation; interferon gamma; messenger RNA; monoclonal antibody; nucleic acid probes; respiratory disorder; tissue /cell culture; transfection; transfection /expression vector; virus protein; western blottings

This application from a young trained otolaryngologist is intended as an initial step in preparation for a career as a academic clinician/scientist. The grant will provide formal training in study design and conduct of an extensive research project and academic course work relevant to the project. Long term goals for the applicant are to be a productive research scientist, competitive for grant funding, in a clinical environment. The training environment is a large teaching hospital that is a clinical campus for a medical school. The hospital offers graduate medical education programs in primary care and medical and surgical specialities. It has a large number of full-time faculty with research grants from both federal and non-federal sources. The applicant's mentors are in the Departments of Otolaryngology and Pediatric Allergy/Immunology, and are full professors at the medical school. The long term goal of the research project is to understand the mechanisms of immune recognition in recurrent respiratory papillomatosis, so that better management of this disease can be achieved. The specific aims will test the hypothesis that human papillomavirus expression results in reduced levels or function of TAP-1 (transporter of antigen-1) and subsequently Class I MHC assembly and expression on the cell surface. The aims are: 1) Determine whether TAP-1 and MHC mRNA and/or proteins are reduced in laryngeal papilloma tissues and cultured cells, compared to normal tissue and cells. 2) Determine whether the TAP-1/MHC-I/calcium binding protein complex functions normally in papilloma cells and whether calcium modulates the complex and TAP-1 and MHC-1 expression differently in normal and papilloma cells. 3) Determine which viral early proteins alter TAP-1 and MHC-1 expression. 4) Determine whether MHC-I levels are increased if TAP-1 levels are increased or its function is bypassed.

这个应用程序从一个年轻的训练有素的耳鼻喉科医生的目的是作为 为学术生涯做准备的第一步 临床医生/科学家。 这笔赠款将提供正规的学习培训 设计和开展广泛的研究项目和学术课程 与项目相关的工作。 申请人的长期目标是 是一个富有成效的研究科学家，有竞争力的赠款资金，在 临床环境。 培训环境是一家大型教学医院， 一所医学院的校园。 该医院提供研究生医疗服务 初级保健、内科和外科教育项目 特色菜。 它有大量的全职教师与研究 来自联邦和非联邦来源的赠款。 申请人的 导师在耳鼻喉科和儿科 过敏/免疫学，并在医学院的全职教授。 该研究项目的长期目标是了解 反复呼吸道感染的免疫识别机制 乳头状瘤病，以便更好地管理这种疾病， 办妥了一批 具体的目标将测试假设，人类 乳头瘤病毒表达导致TAP-1水平或功能降低 （抗原-1的转运蛋白）和随后的I类MHC组装， 在细胞表面表达。 目标是：1）确定是否 喉乳头状瘤中TAP-1和MHC mRNA和/或蛋白表达减少 与正常组织和细胞相比， （二） 确定TAP-1/MHC-I/钙结合蛋白复合物是否 在乳头状瘤细胞中正常发挥作用， 复合物和TAP-1和MHC-1的表达在正常和 乳头状瘤细胞 3)确定哪些病毒早期蛋白改变TAP-1 和MHC-1表达。 4)确定MHC-I水平是否升高 如果TAP-1水平增加或其功能被旁路。

项目成果

Polymorphism of transporter associated with antigen presentation 1 as a potential determinant for severity of disease in recurrent respiratory papillomatosis caused by human papillomavirus types 6 and 11.

与抗原呈递 1 相关的转运蛋白多态性是人乳头瘤病毒 6 型和 11 型引起的复发性呼吸道乳头状瘤病严重程度的潜在决定因素。

• DOI: 10.1086/381764
• 发表时间: 2004
• 期刊: The Journal of infectious diseases
• 作者: Vambutas,Andrea;Bonagura,VincentR;Reed,ElaineF;Abramson,AllanL;Mullooly,Virginia;DeVoti,James;Gjertson,DavidW;Steinberg,BettieM
• 通讯作者: Steinberg,BettieM