Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor
Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor
复制标题
针对肿瘤 H-2 血清学特异性的同种抗血清抑制 T 淋巴细胞介导的肿瘤特异性裂解
DOI：
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发表时间：
1975
影响因子：
15.3
通讯作者：
B. Benacerraf
中科院分区：
文献类型：
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作者：
R. Germain;M. Dorf;B. Benacerraf
经过适当的体内或体外免疫后，会产生细胞毒性 T 淋巴细胞 (CTL)，它能有效杀死与免疫细胞相同的带有特定膜抗原的细胞（参考文献 1 中综述）。这种 CTL 已在小鼠中进行了最彻底的研究，采用了主要组织相容性基因座 H-2 不同的细胞的同种免疫。在这种情况下，CTL 识别的主要细胞表面抗原似乎是携带血清学定义的 H-2 特异性的分子，由 H-2 复合物的 K 和 D 区域编码 (2)。在细胞介导的特异性细胞溶解的其他同系模型中，涉及淋巴细胞脉脑膜炎（LCM）病毒或节肢动物病毒感染的细胞或TNP修饰的淋巴细胞，胸腺来源的细胞也构成了主要的效应细胞类型。当病毒感染或 TNP 修饰的靶细胞在 H-2K 或 H-2D 基因座与效应 CTL 和刺激细胞共享同一性时，后一系统中生成的 CTL 功能最有效 (3-5)。另一组产生 CTL 并发挥重要生物学作用的实验系统是对肿瘤相关抗原 (TAA) 的免疫系统 (6)。 CTL 认可的 TAA 的性质才刚刚开始被理解。最近的几份报告表明 TAA 和 H-2 抗原之间存在理化和/或抗原关系 (7,8)。这些关系，连同上面引用的涉及 H-2K 或 H-2D 基因座产物的 CTL 生成中的遗传限制，表明以下可能性：在某些肿瘤系统中，能够最有效地刺激 CTL 反应的 TAA 可能在结构上与肿瘤表面上的 H-2K 或 H-2D 分子相似或相关。先前已在同种异体模型中证明，针对靶细胞上存在的适当 H-2K 或 H-2D 产物的特异性抗血清可以特异性阻断 CTL 介导的裂解 (1,9)。该报告表明，特定针对靶肿瘤细胞的特定抗H-2同种抗血清可以阻断由同基因肿瘤特异性CTL效应细胞介导的那些靶细胞的裂解。
After appropriate in vivo or in vitro immunization, cytotoxic T lymphocytes (CTL) are generated which efficiently kill cells bearing particular membrane antigens in common with the immunizing cell (reviewed in reference 1). Such CTL have been most thoroughly studied in mice, employing alloimmunization with cells differing at the major histocompatibility locus, H-2. in such cases, the predominant cell surface antigens recognized by the CTL appear to be the molecules carrying the serologically defined H-2 specificities, coded for by the K and D regions of the H-2 complex (2). In other syngeneic models of cell-mediated specific cytolysis, involving lymphocyte chariomeningitis (LCM) virus- or ectromelia virus-infected cells or TNP-modified lymphoid cells, thymus-derived cells also constitute the main effector cell type. The CTL generated in these latter systems function most efficiently when virus-infected or TNP-modified target cells share identitites at the H-2K or H-2D loci with the effector CTL and stimulator cells (3-5). Another set of experimental systems in which CTL are generated and play a significant biological role is that of immunity to tumor-associated antigens (TAA) (6). The nature of the TAA which the CTL recognize is only beginning to be understood. Several recent reports indicated the existence of physiochemical and/or antigenic relationships between TAA and H-2 antigens (7,8). These relationships, together with the genetic restrictions cited above in the generation of CTL involving products of the H-2K or H-2D loci suggested the possibility that in certain tumor systems, the TAA which are able to most effectively stimulate CTL responses might be structurally similar to, or linked with, the H-2K or H- 2D molecules on the tumor surface. It has been previously demonstrated in allogenic models that antisera specific for the appropriate H-2K or H-2D products present on a target cell could specifically block CTL-mediated lysis (1,9). This report demonstrates that certain anti-H-2 alloantisera specific for the target tumor cells can block lysis of those target cells mediated by syngeneic tumor-specific CTL effector cells.