Monach P A, Meredith S C, Siegel C T, Schreiber H
Department of Pathology, University of Chicago, Illinois 60637, USA.
Immunity. 1995 Jan;2(1):45-59. doi: 10.1016/1074-7613(95)90078-0.
Mice immunized against a cancer recognize antigens unique to that cancer, but the molecular structures of such antigens are unknown. We isolated CD4+ T cell clones recognizing an antigen uniquely expressed on the UV-induced tumor 6132A; some clones inhibited the growth of tumors bearing the specific antigen. A T cell hybridoma was used to purify this antigen from nuclear extracts by RP-HPLC and SDS-PAGE using T cell immunoblot assays. A partial amino acid sequence was nearly identical to a sequence in ribosomal protein L9. The cDNA sequence of L9 from 6132A PRO cells differed from the normal sequence at one nucleotide; this mutation encoded histidine instead of leucine at position 47. A synthetic peptide containing this mutation was over 1000-fold more stimulatory of T cells than was the wild-type peptide. These results indicate that this unique tumor antigen is derived from a single amino acid substitution in a cellular protein.
免疫过癌症的小鼠能识别该癌症特有的抗原，但此类抗原的分子结构尚不清楚。我们分离出了能识别紫外线诱导肿瘤6132A上独特表达的抗原的CD4 + T细胞克隆；一些克隆抑制了携带特定抗原的肿瘤的生长。利用T细胞免疫印迹分析，通过反相高效液相色谱（RP-HPLC）和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE），用T细胞杂交瘤从核提取物中纯化该抗原。部分氨基酸序列与核糖体蛋白L9中的一个序列几乎相同。6132A PRO细胞的L9 cDNA序列在一个核苷酸处与正常序列不同；该突变在第47位编码组氨酸而非亮氨酸。含有此突变的合成肽对T细胞的刺激作用比野生型肽强1000多倍。这些结果表明，这种独特的肿瘤抗原源自细胞蛋白中的单个氨基酸取代。
