HLA AND TRANSPLANTATION

本项目的长期目标是鉴定肽 HLA抗原表位，抗体和同种异体免疫是针对这些抗原表位的。 指导。 这些知识将用于设计更准确的方法， 匹配器官移植捐赠者和接受者 虽然一年 近年来，器官移植存活率显著提高， 7年/长期半衰期保持不变。 的 移植物的晚期丢失已被证明是 组织不相容性 现在已知HLA特异性的氨基酸序列， 应该可以确定分子上的哪些位置 免疫原性。 这些信息将有助于开发更多 器官移植的有效匹配措施。 免疫原性表位将通过两种经验方法进行研究：首先， 将分析超过50，000份血清样本，以确定 针对特定的表位，以确定哪些表位是目标， 第二种方法是观察 不相容性导致同种异体移植排斥。 不兼容性 可以检查每种可变氨基酸对其的影响 移植物存活率在实际移植病例中， 加州大学洛杉矶分校和器官移植联合中心 最近关于错配构象表位效应的研究将 延长。 我们将研究某些不相容的 肽不能由宿主MHC呈递，因为缺乏内适性， 最佳状态 分子模拟计算机软件将用于 检查特定的不相容性对MHC分子的影响。 HLA C、DQ和DP基因座的表位的不相容性将被排除。 考察

The long-term objective of this project is to identify the peptide epitopes of HLA against which antibodies and allograft immunity are directed. This knowledge will be used to devise more accurate means of matching organ transplant donors and recipients. Although the one-year organ transplant survival rates have improved dramatically in recent years/ the long-term half life of 7 years has remained unchanged. The late loss of grafts has been shown to be the result of histoincompatibility. Now that the amino acid sequences of HLA specificities are known# it should be possible to ascertain which positions on the molecule are immunogenic. This information will permit the development of more effective measures of matching for organ transplants. The immunogenic epitopes will be studied by two empirical methods: first, more than 50,000 sera samples will be analyzed to identify those that are directed against specific epitopes to see which epitopes are the targets of alloantibodies; the second method will be to see which incompatibilities result in allograft rejections. Incompatibilities for each of the variable amino acids can be examined for their impact on graft survival in actual transplant cases by using data accumulated by the UCLA and UNOS Transplant Registries. Recent studies on the effect of mismatching conformational epitopes will be extended. We will examine the possibility that certain incompatible peptides cannot be presented by the host MHC due to lack of fit within the groove. Molecular modelling computer software will be used to examine the effect of specific incompatibilities on the MHC molecule. Incompatibility for epitopes of the HLA C, DQ and DP loci will be examined.