T细胞在肿瘤免疫中发挥着重要作用,它是通过T细胞抗原受体(TCR)识别肿瘤细胞表面由MHC分子呈递的肿瘤源性多肽,其中细胞毒T淋巴细胞(CTL)是通过识别肿瘤细胞MHC I类分子结合并呈递的多肽。研究表明:CTL识别的多肽常由8～9个氨基酸组成,多肽的呈递受MHC分子等位型的限制,不同的MHC分子具有不同的等位型特异的多肽结合基序(peptidebinding motif)。FBL-3是B6小鼠(H-2~b)源由Friend病毒诱导的小鼠白血病细胞,灭活FBL-3免疫B6小鼠可诱导FBL-3特异CTL产生,从而建立FBL-3特异的免疫应答,保护小鼠免受FBL-3的致瘤性。因此,实验中根据H-2D~b多肽结合基序和Friend病毒gag基因序列,预测出7个可能编码FBL-3抗原多肽的片段。根据预测的结果人工合成了7个九肽(gag1-gag7)。实验结果显示:合成多肽免疫B6小鼠可诱导多肽特异的CTL产生,但用体外实验方法不能诱导初次免疫应答;FBL-3特异CTL可以杀伤gag3,gag5致敏的靶细胞EL-4(H-2~b),但体内实验表明gag3,gag5不象FBL-3一样,它们体内免疫后不能建立有效的抗FBL-3肿瘤免疫效应。表明预测的7个多肽可能不是FBL-3的肿瘤抗原。文中讨论了多肽抗原性预测的复杂性和可能的对策。

T lymphocytes play a very important role in tumor immunity, which recognize tumor antigenic peptide presented by MHC molecules on the surface of tumor cells through T cell receptor ( TCR) . Cytotoxic T lymphocytes kill tumor cells after recognizing antigenic peptide in the cleft of MHC class I molecules. It is now generally accepted that peptides naturally presented by a given MHC class I molecule have a specific motif which is referred to as MHC class I allele-specific consensus motif and that synthetic peptide corresponding to the identified naturally presented antigens exhibit remarkable activity in inducing T-cell responses. FBL-3 is a transplantable Friend virus-induced leukemia of B6 (H-2b) origin,which can induce the CTL against FBL-3 by immunizing B6 mice with atenuated FBL-3.Seven peptides were predicted as candidates of FBL-3 antigenic peptides in the light of H-2Db specific peptide binding motif and gag gene sequence of Friend virus. The synthetic peptides, named gagl to gag7, were obtainted. The results showed that CTL specific to gag3 could be induced by in vivo immunizing B6 mice with gag3 in IFA, but a primary T cell response could not be induced by in vitro immuniztion with the peptides. gag3 and gag5 could be recognized by specific CTL to FBL-3,because the CTLs obviously killed target cells (EL-4) pulsed with gag3 or gag5. Immunization with gag3 and gag5 could not induce an immune response to protect the subsequent challenge of FBL-3 in B6 mice which could be induced by immunizing B6 mice with parental FBL-3 tumor cells. This indicates these 7 synthetic peptides may not be the same antigens of the FBL-3.

国家自然科学基金(39370769)，国家青年自然科学基金(39500133)