Lurquin C, Van Pel A, Mariamé B, De Plaen E, Szikora J P, Janssens C, Reddehase M J, Lejeune J, Boon T
Ludwig Institute for Cancer Research, Brussels, Belgium.
Cell. 1989 Jul 28;58(2):293-303. doi: 10.1016/0092-8674(89)90844-1.
Mutagen treatment of mouse P815 tumor cells produces immunogenic mutants that express new transplantation antigens (tum- antigens) recognized by cytolytic T cells. We found that the gene conferring expression of tum- antigen P91A contains 12 exons, encoding a 60 kd protein lacking a typical N-terminal signal sequence. The sequence shows no significant similarity with sequences in current data bases. A mutation that causes expression of the antigen is located in exon 4; it is the only apparent difference between the normal and the antigenic alleles. A short synthetic peptide corresponding to a region of exon 4 located around this mutation makes P815 cells sensitive to lysis by anti-P91A cytolytic T cells. The mutation creates a strong aggretope enabling the peptide to bind the H-2 Ld molecule. Several secondary tumor cell variants that no longer express tum- antigen P91A were found to carry deletions in the gene.
用诱变剂处理小鼠P815肿瘤细胞可产生免疫原性突变体，这些突变体表达可被细胞毒性T细胞识别的新移植抗原（肿瘤抗原）。我们发现，赋予肿瘤抗原P91A表达的基因包含12个外显子，编码一种60kd的蛋白质，该蛋白质缺乏典型的N端信号序列。该序列与当前数据库中的序列没有显著相似性。导致抗原表达的突变位于外显子4中；它是正常等位基因和抗原等位基因之间唯一明显的差异。对应于该突变周围外显子4区域的短合成肽使P815细胞对抗P91A细胞毒性T细胞的裂解敏感。该突变产生了一个强聚集表位，使该肽能够结合H-2 Ld分子。发现几个不再表达肿瘤抗原P91A的继发性肿瘤细胞变体在该基因中存在缺失。
