MOLECULAR/CELLULAR BASIS OF CARDIAC ALLOGRAFT REJECTION

这项研究提案的主要目标是确定 参与免疫识别过程的分子成分 同种异体排斥反应。移植物排斥反应是由T细胞引起的。 受体通过克隆识别异种移植物的抗原- 表达的TCRs。这一识别过程的基础是形成 由TCR、MHC分子组成的三分子络合物 受体和/或供体类型)，以及来自代谢的多肽 处理过的移植物抗原。免疫过程中这种复合体的形成 对移植物的反应启动了一系列细胞内和细胞间的 导致移植物被破坏的反应。因此，澄清 三分子复合体的性质和随后发生的事件 参与移植排斥反应不仅会拓宽我们的理解 但也可能提供一种手段来诱导嫁接- 特定容忍度。 这项建议的具体目标包括： 1.从中国分离的GIL对TCR谱系使用情况的表征 在不同品种的大鼠组合中进行的同种异体心脏移植 组织相容性抗原的范围。 2.建立特异性GIL的T细胞系和/或克隆 对移植物抗原的反应性及其在调节中的作用 心脏移植后的排斥反应。 3.识别作为移植物靶标的移植物抗原- 反应性T细胞及其在排斥反应中的作用分析 反应。

The primary objectives of this research proposal are to identify the molecular components of the immune recognition process involved in allograft rejection. Graft rejection is initiated by T cells of the recipient recognizing antigens of the foreign graft through clonally- expressed TCRs. The basis of this recognition process is the formation of a trimolecular complex consisting of the TCR, MHC molecule (of the recipient and/or donor type), and a peptide derived from metabolically processed graft antigens. The formation of this complex during immune response to the graft initiates a set of intra- and intercellular reactions that result in destruction of the graft. Hence, elucidation of the nature of the trimolecular complex and the subsequent events involved in the graft rejection will not only broaden our understanding of the rejection process, but may also provide a means to induce graft- specific tolerance. The Specific Aims of this proposal include: 1. Characterization of the TCR repertoire usage by GILs isolated from cardiac allografts performed in rat strain combinations disparate for range of histocompatibility antigens. 2. Establishment of T-cell lines and/or clones from GILs with specific reactivity to graft antigens and examination of their role in mediating cardiac graft rejection following adoptive transfer. 3. Identification of graft antigens that serve as targets for graft- reactive T cells and the analysis of their role in the rejection reaction.