Development of HLA bound peptitides which have supressive activity.

有许多疾病是由免疫反应异常引起的。为了开发与人类白细胞抗原分子结合的非刺激性多肽类似物，我们研究了人类白细胞抗原与多肽的相互作用。研究了人类白细胞抗原-DP9(DPA1*0201/DPB1*0901)分子与12型(SS95/12)链球菌M蛋白的相互作用。共鉴定出7个受人类白细胞抗原-DP9分子限制的抗原肽。比较这些多肽的氨基酸序列，发现了与HLA-DP9特异的结合基序，这与与HLA-DR分子的结合基序不同。在分析人类白细胞抗原-DR51和-DQ6转基因小鼠对合成肽的反应时，我们发现DR51和DQ6转基因小鼠对合成肽有显著的T细胞应答。提示人类白细胞抗原转基因小鼠可作为体内检测人类白细胞抗原分子功能的有用工具。本研究还建立了人类白细胞抗原A、DR、DQ、DP等位基因的PCR/SSOP分型方法，发现了几个新的等位基因。利用这种方法，我们确定了几个自身免疫性疾病的易感基因。

There are many diseases caused by abnormal immune responses. To develop the non stimulatory peptide analog that binds to HLA molecule, we investigated the HLA-peptide interactions. Interaction of HLA-DP9 (DPA1*0201/DPB1*0901) molecule and M protein of serotype 12 (SS95/12) streptococcus has been investigated. Seven antigenic peptides restricted by the HLA-DP9 molecule were identified. Comparison of the amino acid sequences among these peptides revealed HLA-DP9-specific binding motif, which differs from the binding motif to the HLA-DR molecules. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to the peptides. This indicated that HLA transgenic mouse should be a useful tool to examine the function of HLA molecules in vivo. We also developed the DNA typing method using PCR/SSOP analysis for HLA-A,HLA-DR,DQ and DP alleles, and found several new alleles. Using this method we determined several susceptible genes for autoimmune disease.