MOLECULAR IMMUNOLOGY OF MINOR HISTOCOMPATIBILITY ANTIGEN

描述（改编自研究者摘要）： 该项目的长期目标是确定 MHC介导移植物抗宿主病的免疫反应 完全相同的无关骨髓移植研究者还将 定义针对同种异体抗原的特异性免疫抑制方案 而不损害所有T细胞的功能。研究者 希望确定免疫优势的机制，以少数 组织相容性（mH）抗原的研究，并开发新的 诱导移植耐受的方案。这背后的基本原理 研究表明，对mH抗原免疫优势的分子基础 是很难理解的。此外，目前的免疫方案- 抑制作用影响所有活化T细胞或T细胞亚群，从而 麻痹对病原体的免疫反应研究者将测试2 假设：首先，免疫优势在很大程度上取决于 CTL前体频率、肽对MHC的亲和力和 TcR的MHC/肽复合物。第二个要检验的假设 对mH抗原的免疫可以被可溶性四聚体抑制， I类MHC分子呈递mH Ag特异性表位。的 期望在项目顺利完成后， 研究者将确定免疫优势的分子基础 一般来说，抗原引起CTL应答，并且新的 在没有一般抑制的情况下下调CTL应答的方案将 发展。

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.