MOLECULAR IMMUNOLOGY OF MINOR HISTOCOMPATIBILITY ANTIGEN

次要组织相容性抗原的分子免疫学

• 批准号: 6330085
• 负责人: SEBASTIAN JOYCE
• 金额: $ 25.92万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6330085
• 关键词: MHC class I antigen; T cell receptor; cytotoxic T lymphocyte; gene expression; histocompatibility antigens; laboratory mouse; leukocyte activation /transformation; minor histocompatibility loci; tissue /cell culture; transplantation immunology

DESCRIPTION (Adapted from the investigator's abstract): The long term goal of this project is to define the molecular basis of the immune responses that mediate graft versus host disease in MHC identical unrelated bone marrow transplants. The investigator will also define protocols for specific suppression of immunity to allo-antigens without compromising the function of all T cells. The investigator wishes to define the mechanism of immunodominance to minor histocompatibility (mH) antigens in molecular terms and to develop novel protocols to induce transplant tolerance. The rationale behind this research is that the molecular basis of immunodominance to mH antigens is poorly understood. Additionally, current protocols for immuno- suppression affect all activated T cells or T-cell subsets, thereby paralyzing immune responses to pathogens. The investigator will test 2 hypotheses: First, that immunodominance is determined in great part by CTL precursor frequency, affinity of peptide to MHC and the affinity of MHC/peptide complexes for the TcR. The second hypothesis to be tested is that immunity to mH antigens can be inhibited by soluble tetrameric class I MHC molecules presenting a mH Ag-specific epitope. The expectation is that upon successful completion of the project, the investigator will have defined the molecular basis of immunodominance to antigens that elicit CTL responses in general, and that a novel protocol to down regulate CTL responses without general suppression will be developed.

描述(改编自调查人员的摘要)： 这个项目的长期目标是定义分子基础 MHC中介导移植物抗宿主病的免疫反应 相同的无血缘关系的骨髓移植。调查员还将 确定特定抑制同种抗原免疫的方案 而不会损害所有T细胞的功能。调查员 希望定义未成年人免疫优势的机制 组织相容性(MH)抗原在分子水平上的应用及其开发新途径 诱导移植耐受的方案。这背后的理由是 研究表明，对MH抗原免疫优势的分子基础 人们对此知之甚少。此外，目前的免疫方案- 抑制会影响所有激活的T细胞或T细胞亚群，从而 瘫痪对病原体的免疫反应。调查员将测试2 假设：首先，免疫优势在很大程度上是由 CTL前体频率、多肽与MHC的亲和力及其与MHC的亲和力 TCR的MHC/多肽复合体。需要检验的第二个假设 对MH抗原的免疫可被可溶性四聚体抑制 I类MHC分子呈现MH抗原特异性表位。这个 预计在项目成功完成后， 研究人员将会定义免疫优势的分子基础 一般能引起CTL反应的抗原，而一种新的 在不全面抑制的情况下下调CTL反应的协议将 被开发出来。