Uyttenhove C, Godfraind C, Lethé B, Amar-Costesec A, Renauld J C, Gajewski T F, Duffour M T, Warnier G, Boon T, Van den Eynde B J
Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels, Belgium.
Int J Cancer. 1997 Jan 27;70(3):349-56. doi: 10.1002/(sici)1097-0215(19970127)70:3<349::aid-ijc17>3.0.co;2-a.
Tumor antigen P815AB is recognized by cytolytic T lymphocytes (CTL) on mouse mastocytoma P815. This antigen is encoded by P1A, a gene activated in several tumors but silent in normal tissues except for testis and placenta. Notwithstanding the expression of P1A in testis, we found that male mice mounted P815AB-specific CTL responses as efficiently as females. The responding males remained fertile and no autoimmune lesions were observed in their testes. By immunohistochemistry with a rabbit antiserum directed against the P1A protein, we identified spermatogonia as the testicular cells expressing P1A. The absence of MHC class-I molecules on spermatogonia could be one of the mechanisms of protection against testicular autoimmunity, as the antigenic peptide should not be displayed at the cell surface. Human genes MAGE, BAGE and GAGE, which also code for tumor antigens recognized by autologous CTL, are not expressed in normal tissues other than testis. The results obtained in mice with antigen P815AB suggest that immunization of human males with such antigens will not generate autoimmune side-effects. Although P1A is strongly expressed in placenta, we also found that gestation did not prevent generation of CTL responses against antigen P815AB, and that such CTL responses did not affect gestation outcome. We identified labyrinthine trophoblasts as the placental cells expressing P1A. Again, the absence of MHC class-I molecules on these cells provides a plausible explanation for placental protection, although other mechanisms may also play a role.
肿瘤抗原P815AB可被小鼠肥大细胞瘤P815上的细胞毒性T淋巴细胞（CTL）识别。该抗原由P1A编码，P1A基因在多种肿瘤中被激活，但在除睾丸和胎盘外的正常组织中沉默。尽管P1A在睾丸中表达，但我们发现雄性小鼠产生P815AB特异性CTL反应的效率与雌性小鼠相同。有反应的雄性小鼠仍保持生育能力，且在其睾丸中未观察到自身免疫性病变。通过用针对P1A蛋白的兔抗血清进行免疫组织化学，我们确定精原细胞是睾丸中表达P1A的细胞。精原细胞上缺乏MHC I类分子可能是防止睾丸自身免疫的机制之一，因为抗原肽不应在细胞表面展示。人类基因MAGE、BAGE和GAGE也编码被自体CTL识别的肿瘤抗原，它们在除睾丸外的正常组织中不表达。用抗原P815AB在小鼠中获得的结果表明，用此类抗原免疫人类男性不会产生自身免疫副作用。尽管P1A在胎盘中强烈表达，但我们还发现妊娠并未阻止针对抗原P815AB的CTL反应的产生，且此类CTL反应不影响妊娠结局。我们确定迷路滋养层细胞是胎盘中表达P1A的细胞。同样，这些细胞上缺乏MHC I类分子为胎盘保护提供了一个合理的解释，尽管其他机制可能也起作用。
