Wang R F, Appella E, Kawakami Y, Kang X, Rosenberg S A
National Cancer Institute, Bethesda, Maryland 20892, USA.
J Exp Med. 1996 Dec 1;184(6):2207-16. doi: 10.1084/jem.184.6.2207.
The infusion of TIL586 along with interleukin-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31-restricted CTL clone derived from the TIL586 cell line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide. Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.
将TIL586与白细胞介素-2一同注入患有转移性黑色素瘤的自体患者体内，导致肿瘤出现客观消退。先前已分离出一个编码被TIL586识别的肿瘤抗原的基因，并证明其编码gp75或TRP-1。在此我们报告，TRP-2被鉴定为第二个被源自TIL586细胞系的HLA-A31限制性CTL克隆识别的肿瘤抗原。基于对截短的TRP-2 cDNA的识别研究以及HLA-A31结合基序，随后从TRP-2的编码区鉴定出肽LLPGGRPYR表位。该表位肽在1 nM肽浓度下能够使靶细胞对CTL克隆的裂解敏感。尽管一些修饰肽能够被CTL克隆识别，但未发现有比亲本肽更能被T细胞识别的肽。与其他黑色素瘤分化抗原一样，TRP-2仅在黑色素瘤、黑素细胞和视网膜中表达，而在测试的其他人体组织中不表达。
