von Hoegen P, Altevogt P, Schirrmacher V
Institut für Immunologie und Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
Cell Immunol. 1987 Oct 15;109(2):338-48. doi: 10.1016/0008-8749(87)90317-0.
The specific immune response against syngeneic tumors by T cells is dependent on the existence of tumor-associated transplantation antigens (TATA). In the case of the chemically induced DBA/2-derived lymphoma Eb and its highly metastatic variant ESb the immunogenicity of these antigens is not sufficient to prevent tumor growth. Therefore we tested in two systems the influence of additional antigens as possible helper determinants for the generation of tumor-specific immune responses. In the Eb tumor system additional antigens were induced by mutagenization. The frequency of cytotoxic T lymphocytes (CTL) in response to mutagenized Eb cells was higher than that in response to untreated Eb cells. Fine specificity analysis revealed there there was no increase in the CTL response against the original TATA, but an activation of additional CTL clones responding to mutagen-induced antigens. In the ESb tumor system we tested the effect of additional recognition of minor histocompatibility antigens on the frequency of TATA-specific CTL. Transplantation of ESb tumor cells into B10.D2 mice, which are H-2-identical but differ in minor antigens, results in strong tumor rejection responses. In a limiting dilution mixed-leukocyte-tumor microculture system it was found that the minor antigens are recognized at the clonal level as independent antigens. The overall frequency of anti-tumor CTL in ESb-immunized B10.D2 mice was about 1/3000. Among these, the frequency of TATA-specific CTL was 1/16,709 and thus not significantly different from that of syngeneic DBA/2 mice. Thus neither minor antigens nor mutagen-induced antigens acted in the Eb/ESb tumor system as helper determinants and did not increase the frequency of tumor-specific CTLs.
T细胞针对同基因肿瘤的特异性免疫反应取决于肿瘤相关移植抗原（TATA）的存在。就化学诱导的源自DBA/2的淋巴瘤Eb及其高转移性变体ESb而言，这些抗原的免疫原性不足以阻止肿瘤生长。因此，我们在两个系统中测试了额外抗原作为肿瘤特异性免疫反应产生的可能辅助决定因素的影响。在Eb肿瘤系统中，通过诱变诱导额外抗原。针对诱变后的Eb细胞产生的细胞毒性T淋巴细胞（CTL）频率高于针对未处理的Eb细胞产生的频率。精细特异性分析表明，针对原始TATA的CTL反应没有增加，但对诱变诱导抗原产生反应的额外CTL克隆被激活。在ESb肿瘤系统中，我们测试了对次要组织相容性抗原的额外识别对TATA特异性CTL频率的影响。将ESb肿瘤细胞移植到H-2相同但次要抗原不同的B10.D2小鼠中，会导致强烈的肿瘤排斥反应。在有限稀释混合白细胞-肿瘤微培养系统中发现，次要抗原在克隆水平上被识别为独立抗原。在ESb免疫的B10.D2小鼠中，抗肿瘤CTL的总体频率约为1/3000。其中，TATA特异性CTL的频率为1/16,709，因此与同基因DBA/2小鼠的频率没有显著差异。因此，在Eb/ESb肿瘤系统中，次要抗原和诱变诱导抗原均未作为辅助决定因素起作用，也未增加肿瘤特异性CTL的频率。
