HLA AND TRANSPLANTATION

这个项目的长期目标是鉴定多肽 针对抗体和同种异体移植免疫的人类白细胞抗原表位 导演。这些知识将被用来设计出更准确的方法 匹配器官移植捐赠者和接受者。虽然一年制 近年来，器官移植存活率有了显著提高。 年/7年的长期半衰期保持不变。这个 移植物的晚期丢失已被证明是由 组织不相容。 既然已经知道了人类白细胞抗原特异性的氨基酸序列#it 应该可以确定分子上的哪些位置 免疫原性。这些信息将允许开发更多 器官移植配型的有效措施。 免疫原性表位将通过两种经验方法进行研究：第一， 将对50,000多份血清样本进行分析，以确定哪些 针对特定表位，以查看哪些表位是目标 同种抗体；第二种方法是看看哪一种 不相容会导致同种异体移植排斥反应。的不兼容性 每一种可变氨基酸都可以被检查它们对 使用以下积累的数据计算实际移植病例的移植物存活率 加州大学洛杉矶分校和联合国大学移植登记处。 最近关于构象表位错配的影响的研究将 是延伸的。我们将研究某些不兼容的可能性 多肽不能由宿主MHC呈递，因为它不适合在 这是最棒的。分子模拟计算机软件将用于 检查特定的不相容对MHC分子的影响。 人类白细胞抗原C、DQ和DP基因座表位的不相容 检查过了。

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.