Fisk B, Blevins T L, Wharton J T, Ioannides C G
Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
J Exp Med. 1995 Jun 1;181(6):2109-17. doi: 10.1084/jem.181.6.2109.
Synthetic peptide analogues of sequences in the HER-2 protooncogene (HER-2) were selected based on the presence of HLA-A2.1 anchor motifs to identify the epitopes on HER-2 recognized by ovarian tumor-reactive CTL. 19 synthetic peptides were evaluated for recognition by four HLA-A2 ovarian-specific cytotoxic T lymphocyte (CTL) lines obtained from leukocytes associated with ovarian tumors. The nonapeptide E75 (HER-2, 369-377:KIFGSLAFL) was efficient in sensitizing T2 cells for lysis by all four CTL lines. This peptide was specifically recognized by cloned CD8+ CTL isolated from one of the ovarian-specific CTL lines. E75-pulsed T2 cells inhibited lysis by the same CTL clone of both an HLA-A2+ HER-2high ovarian tumor and a HER-2high cloned ovarian tumor line transfected with HLA-A2, suggesting that this or a structurally similar epitope may be specifically recognized by these CTL on ovarian tumors. Several other HER-2 peptides were recognized preferentially by one or two CTL lines, suggesting that both common and private HER-2 epitopes may be immunogenic in patients with ovarian tumors. Since HER-2 is a self-antigen, these peptides may be useful for understanding mechanisms of tumor recognition by T cells, immunological tolerance to tumor, and structural characterization of tumor antigens.
基于HLA - A2.1锚定基序的存在，选择HER - 2原癌基因（HER - 2）序列的合成肽类似物，以鉴定卵巢肿瘤反应性CTL识别的HER - 2上的表位。对19种合成肽进行评估，以检测其是否能被从与卵巢肿瘤相关的白细胞中获得的4种HLA - A2卵巢特异性细胞毒性T淋巴细胞（CTL）系识别。九肽E75（HER - 2，369 - 377：KIFGSLAFL）能有效使T2细胞对所有4种CTL系的裂解敏感。该肽被从其中一种卵巢特异性CTL系中分离出的克隆CD8 + CTL特异性识别。用E75脉冲处理的T2细胞抑制了来自同一CTL克隆对HLA - A2 + HER - 2高表达卵巢肿瘤和转染了HLA - A2的HER - 2高表达克隆卵巢肿瘤系的裂解，这表明这些CTL可能在卵巢肿瘤上特异性识别这个或结构相似的表位。其他几种HER - 2肽优先被一两种CTL系识别，这表明常见和独特的HER - 2表位在卵巢肿瘤患者中可能都具有免疫原性。由于HER - 2是一种自身抗原，这些肽可能有助于理解T细胞识别肿瘤的机制、对肿瘤的免疫耐受以及肿瘤抗原的结构特征。
