Tsuyuoka K, Yago K, Hirashima K, Ando S, Hanai N, Saito H, Yamasaki K M, Takahashi K, Fukuda Y, Nakao K, Kannagi R
Laboratory of Experimental Pathology, Research Institute, Aichi Cancer Center, Nagoya, Japan.
J Immunol. 1996 Jul 15;157(2):661-9.
The stage-specific embryonic Ag-1 (SSEA-1) is a carbohydrate Ag and regarded as an onco-developmental Ag. Sialyl SSEA-1 Ag, the sialylated form of SSEA-1, is frequently expressed in human cancer cells as well as in murine cancer cells. A mAb, FH-6, was shown to specifically recognize the Ag. We have generated five anti-Id Abs directed to the paratope-related idiotopes of the FH-6 Ab. One of these anti-Id Abs, Id-F2, increased the survival of host mice that were inoculated with Meth-A cells expressing the sialyl SSEA-1 Ag. To clarify the exact mechanism underlying the antitumor effect of the anti-Id Ab, we established a T cell line that recognized Id-F2 in association with MHC class II molecules. The T cell line was CD4+V beta 8+, and produced IL-2, exhibiting helper activity for B cells. The VH CDR2 region of the Id-F2 amino acid sequences turned out to be strongly immunogenic to T cells. When the immune complexes, consisting of the sialyl SSEA-1 Ag, FH-6, and Id-F2, were formed at the Meth-A cell-surface, the T cell line showed a strong proliferative response. The possible roles played by such T cell subsets in the anti-tumor effect are discussed.
阶段特异性胚胎抗原-1(SSEA-1)是一种碳水化合物抗原,被视为一种肿瘤发生发展相关抗原。唾液酸化SSEA-1抗原(SSEA-1的唾液酸化形式)在人类癌细胞和鼠类癌细胞中均频繁表达。一种单克隆抗体FH-6被证明能特异性识别该抗原。我们制备了五种针对FH-6抗体互补决定区相关独特型的抗独特型抗体。其中一种抗独特型抗体Id-F2可提高接种表达唾液酸化SSEA-1抗原的Meth-A细胞的宿主小鼠的存活率。为阐明抗独特型抗体抗肿瘤作用的确切机制,我们建立了一种能与MHC II类分子结合识别Id-F2的T细胞系。该T细胞系为CD4+Vβ8+,可产生白细胞介素-2,对B细胞表现出辅助活性。Id-F2氨基酸序列的VH CDR2区域对T细胞具有很强的免疫原性。当在Meth-A细胞表面形成由唾液酸化SSEA-1抗原、FH-6和Id-F2组成的免疫复合物时,该T细胞系表现出强烈的增殖反应。文中讨论了此类T细胞亚群在抗肿瘤作用中可能发挥的作用。