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

在TCR、MHC分子和抗原的多肽片段之间形成三分子复合体后，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体的形成至关重要。我们已经报道了鸽子细胞色素c相关多肽以等位基因特异性的方式与小鼠MHC II类分子结合。为了检测与人类II类分子结合的多肽，我们尝试建立了DR转基因小鼠。由于我们通过PCR技术在一些小鼠体内检测到了注射的DNA，所以我们正在测试DR分子在小鼠不同组织中的表达。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Sasazuki博士提供的DQw6转基因小鼠的T细胞。在第46位携带精氨酸，在第54位携带丙氨酸的多肽，已被确定为与DQw6分子(AegRSYTVANKAKGIT)结合的结合表位。此外，我们还发现了一个由流感病毒血凝素123-138(EGFTWTGVTQNGGSNA)结合到DQw6分子上的肽。我们还报道了携带小鼠MHC结合基序的鸽子细胞色素c相关肽与流感病毒的血凝素具有替代的表位残基(结合TCR的位点)，可以刺激小鼠对流感病毒的免疫应答(卡盒理论)。由于已经出现了与人MHC分子结合的基序，利用盒理论制备的针对流感病毒的多肽疫苗将在人类身上发挥作用。

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.