Slager Elisabeth H, Honders M Willy, van der Meijden Edith D, van Luxemburg-Heijs Simone A P, Kloosterboer Freke M, Kester Michel G D, Jedema Inge, Marijt W A Erik, Schaafsma M Ron, Willemze Roel, Falkenburg J H Frederik
Department of Hematology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Blood. 2006 Jun 15;107(12):4954-60. doi: 10.1182/blood-2005-09-3883. Epub 2006 Feb 23.
Characterization of the antigens recognized by tumor-reactive T cells isolated from patients successfully treated with allogeneic HLA-matched hematopoietic stem cell transplantation (SCT) can lead to the identification of clinically relevant target molecules. We isolated tumor-reactive cytotoxic CD8(+) T-cell (CTL) clones from a patient successfully treated with donor lymphocyte infusion for relapsed multiple myeloma after allogeneic HLA-matched SCT. Using cDNA expression cloning, the target molecule of an HLA-B7-restricted CTL clone was identified. The CTL clone recognized a minor histocompatibility antigen produced by a single nucleotide polymorphism (SNP) in the angiogenic endothelial-cell growth factor-1 (ECGF1) gene also known as thymidine phosphorylase. The SNP leads to an Arg-to-His substitution in an alternatively translated peptide that is recognized by the CTL. The ECGF1 gene is predominantly expressed in hematopoietic cells, although low expression can also be detected in other tissues. The patient from whom this CTL clone was isolated had mild graft-versus-host disease despite high numbers of circulating ECGF-1-specific T cells as detected by tetramer staining. Because solid tumors expressing ECGF-1 could also be lysed by the CTL, ECGF-1 is an interesting target for immunotherapy of both hematologic and solid tumors.
对从接受异基因 HLA 匹配造血干细胞移植（SCT）并成功治疗的患者中分离出的肿瘤反应性 T 细胞所识别抗原进行表征，可有助于鉴定临床相关的靶分子。我们从一名接受供体淋巴细胞输注成功治疗异基因 HLA 匹配 SCT 后复发的多发性骨髓瘤患者中分离出肿瘤反应性细胞毒性 CD8(+) T 细胞（CTL）克隆。利用 cDNA 表达克隆技术，鉴定出一个 HLA - B7 限制性 CTL 克隆的靶分子。该 CTL 克隆识别由血管生成内皮细胞生长因子 -1（ECGF1，也称为胸苷磷酸化酶）基因中的单核苷酸多态性（SNP）产生的一种次要组织相容性抗原。该 SNP 导致一个在可变翻译肽段中的精氨酸到组氨酸的替换，此肽段被 CTL 识别。ECGF1 基因主要在造血细胞中表达，尽管在其他组织中也能检测到低水平表达。分离出该 CTL 克隆的患者尽管通过四聚体染色检测到大量循环的 ECGF -1 特异性 T 细胞，但仍有轻度移植物抗宿主病。由于表达 ECGF -1 的实体瘤也可被该 CTL 裂解，因此 ECGF -1 是血液系统肿瘤和实体瘤免疫治疗的一个有意义的靶点。
