The T cell response to rapidly evolving HIV antigens

T 细胞对快速进化的 HIV 抗原的反应

• 批准号: 6740059
• 负责人: DANIEL Garrett KAVANAGH
• 金额: $ 4.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740059
• 关键词: AIDS; HIV infections; T lymphocyte; antigen presenting cell; cellular immunity; clinical research; cytotoxic T lymphocyte; dendritic cells; enzyme linked immunosorbent assay; human immunodeficiency virus 1; human subject; immune response; polymerase chain reaction; postdoctoral investigator; virus antigen

DESCRIPTION (provided by applicant): Antiviral CD8+ T cells play an important role in initial control of HIV replication and presumably help delay the onset of AIDS in HIV infected individuals. In order to understand the role of antiviral CD8+ T cells in immune protection, it will be necessary to comprehensively characterize the specificities CD8+ T cells in HIV-infected patients. A major obstacle to this goal is the high degree of genetic variability among HIV clinical isolates from different individuals. Most current techniques to screen T cell specificities rely on reference strain antigens or synthetic peptides representing a consensus sequence. These methods may underestimate T cell response due to genetic divergence between the assay antigen and autologous virus. This proposal describes an approach, based on transfection of antigen presenting cells with synthetic mRNA, for efficient screening of patient CDS+ T cell responses to autologous HIV antigens. This method will be used to compare the T cell responses to autologous and consensus antigens in chronic HIV infection.

描述（由申请人提供）：抗病毒 CD8+ T 细胞在 HIV 复制的初始控制中发挥着重要作用，并且可能有助于延缓 HIV 感染者的 AIDS 发病。为了了解抗病毒 CD8+ T 细胞在免疫保护中的作用，有必要全面表征 HIV 感染者中 CD8+ T 细胞的特异性。实现这一目标的一个主要障碍是不同个体的艾滋病毒临床分离株之间存在高度遗传变异性。目前大多数筛选 T 细胞特异性的技术依赖于参考株抗原或代表共有序列的合成肽。由于测定抗原和自体病毒之间的遗传差异，这些方法可能会低估 T 细胞反应。该提案描述了一种基于用合成 mRNA 转染抗原呈递细胞的方法，用于有效筛选患者 CDS+ T 细胞对自体 HIV 抗原的反应。该方法将用于比较慢性 HIV 感染中 T 细胞对自体抗原和共有抗原的反应。