Detection of amino acid motifs on the agretopes of antigens highly bound to MHC molecules

在TCR、MHC分子和抗原肽片段之间形成三分子复合物后，T细胞被激活。在这种情况下，抗原肽和MHC分子之间的结合对于三分子复合物的构成至关重要。我们已经报道了鸽子细胞色素c相关肽以等位基因特异性的方式取代了与小鼠MHC II类分子结合的agretopes（与MHC分子结合的位点）。为了检测与人II类分子结合的肽，我们尝试建立DR转基因小鼠。由于我们用PCR技术检测了一些小鼠注射的dna，我们正在测试DR分子在小鼠各组织中的表达。在另一项工作中，我们发现鸽子细胞色素c相关肽与DQw6分子结合，并激活了由Sasazuki博士提供的DQw6转基因小鼠中的T细胞。在46号位置携带精氨酸和54号位置携带丙氨酸的肽被确定为与DQw6分子结合的附着位（AEGRSYTVANKAKGIT）。此外，我们发现一种由流感病毒血凝素123-138 （EGFTWTGVTQNGGSNA）组成的肽与DQw6分子结合。我们还报道了鸽子细胞色素c相关肽携带小鼠MHC结合基序与流感病毒血凝素取代表位残基（与TCR结合的位点）可以刺激小鼠对流感病毒的免疫反应（卡式理论）。由于结合人MHC分子的基序已经出现，利用卡式理论制备的流感病毒肽疫苗将对人有效。

After constitution of tri-molecular complexes among TCR, MHC molecules,and peptide fragments of antigens, T cells are activated. In this event, binding between antigen peptides and MHC molecules is critical for constitution of the tri-molecular complex. we have reported pigeon cytochrome c related peptides substituted at agretopes (sites bound to MHC molecules) bound to murine MHC class II molecules in an allele specific manner. In order to detect peptides bound to human class II molecules we tried to establish DR transgenic mice. Since we detected the injected DNAs in some mice by PCR technique, we are testing expression of the DR molecules in various tissues of the mice.In another work we found that pigeon cytochrome c related peptides bound to DQw6 molecules and activated T cells in the DQw6 transgenic mice kindly provided by Dr. Sasazuki. Peptides carrying arginine at position 46 and alanine at position 54 which had been determined as agretopes bound to DQw6 molecules (AEGRSYTVANKAKGIT). Further, we found a peptide consisted of influenza virus haemagglutinin 123-138 (EGFTWTGVTQNGGSNA) bound to DQw6 molecules.We have also reported that pigeon cytochrome c related peptides carrying the murine MHC binding motif with substituted epitopic residues (sites bound to TCR) to haemagglutinin of influenza virus can stimulate immune responses to influenza virus in mice (cassette theory). Since the motif bound to human MHC molecules has been appeared, peptide vaccines prepared by the cassette theory to influenza virus will be effective in human.