Yoshitomi Tomomi, Hirahara Kazuki, Kawaguchi Junko, Serizawa Nobufusa, Taniguchi Yoshifumi, Saito Saburo, Sakaguchi Masahiro, Inouye Sakae, Shiraishi Akio
Sankyo Co., Ltd, Tokyo, Japan, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Immunology. 2002 Dec;107(4):517-22. doi: 10.1046/j.1365-2567.2002.01534.x.
It has been demonstrated in detail that administration of a dominant T-cell determinant to animals induces activation or immunological tolerance of T cells. However, it has not been determined whether multiple T-cell determinants, when integrated into a single peptide, retain their potential to induce T-cell activation and tolerance. We prepared a synthetic peptide comprising three T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen antigens, and investigated the immunogenicity and tolerogenicity of each T-cell determinant in the linked peptide by means of lymph node cell proliferation assays using mice. Lymph node cells from mice immunized with each of the three T-cell determinants proliferated against the linked peptide in a dose-dependent manner, similar to that of the immunized peptide. Lymph node cells from mice immunized with the linked peptide proliferated against all of the three T-cell determinants. In addition, the degree of proliferation against the three T-cell determinants occurred according to their original immunogenicity, as observed in the native protein antigens. Oral administration of the linked peptide to mice before they were immunized with Cry j 1 and Cry j 2 inhibited lymph node cell proliferation against the three T-cell determinants, depending on the dose of the linked peptide administered. In conclusion, it was demonstrated that three T-cell determinants retain their original immunogenicity and tolerogenicity in a linked peptide comprising them.
已详细证明,向动物施用显性T细胞决定簇可诱导T细胞活化或免疫耐受。然而,尚未确定当多个T细胞决定簇整合到单个肽中时,它们是否仍具有诱导T细胞活化和耐受的潜力。我们制备了一种包含日本雪松主要花粉抗原Cry j 1和Cry j 2的三个T细胞决定簇的合成肽,并通过使用小鼠的淋巴结细胞增殖试验研究了连接肽中每个T细胞决定簇的免疫原性和耐受性。用三个T细胞决定簇中的每一个免疫的小鼠的淋巴结细胞以剂量依赖性方式针对连接肽增殖,类似于免疫肽的增殖方式。用连接肽免疫的小鼠的淋巴结细胞针对所有三个T细胞决定簇增殖。此外,正如在天然蛋白质抗原中观察到的那样,针对三个T细胞决定簇的增殖程度根据其原始免疫原性而发生。在用Cry j 1和Cry j 2免疫小鼠之前,向小鼠口服连接肽可抑制淋巴结细胞针对三个T细胞决定簇的增殖,这取决于所施用的连接肽的剂量。总之,已证明三个T细胞决定簇在包含它们的连接肽中保留其原始免疫原性和耐受性。