D'Souza S, Rimoldi D, Líenard D, Lejeune F, Cerottini J C, Romero P
Multidisciplinary Oncology Center, CHUV, Lausanne, Switzerland.
Int J Cancer. 1998 Dec 9;78(6):699-706. doi: 10.1002/(sici)1097-0215(19981209)78:6<699::aid-ijc6>3.0.co;2-u.
Melan-A/MART-1 is a melanoma differentiation antigen that is recognized by a high proportion of cytolytic T lymphocyte (CTL) clones derived from human leukocyte antigen (HLA)-A2+ melanoma patients. Whereas peptide Melan-A/ MART-1(27-35) was originally defined as the immunodominant CTL epitope, we have previously reported that peptide Melan-A/MART-1(26-35) was recognized more efficiently by the majority of tumor-reactive CTL clones. As demonstrated here, CTL populations generated from blood lymphocytes of either melanoma patients or healthy individuals after in vitro stimulation with peptide Melan-A/MART-1(26-35) killed specifically HLA-A2+ Melan-A+ allogeneic melanoma cells, thus suggesting their potential use in adoptive immunotherapy. We characterized the surface phenotype of the circulating CTL precursors (CTLp), which respond to in vitro stimulation with peptide Melan-A/MART-1(26-35). In melanoma patients, these CTLp predominantly expressed the CD45RO memory marker. In contrast, they were mainly, although not exclusively, found in the CD45RA subpopulation of CD8 T cells in healthy individuals. The demonstration that Melan-A/MART-1-specific CTLp in peripheral blood lymphocytes from HLA-A2+ patients with metastatic melanoma express a memory phenotype provides direct evidence that in vivo priming of this antigen may occur during tumor progression.
黑色素瘤抗原A/MART-1是一种黑色素瘤分化抗原，可被源自人类白细胞抗原（HLA）-A2+黑色素瘤患者的高比例细胞毒性T淋巴细胞（CTL）克隆识别。虽然肽段Melan-A/MART-1(27-35)最初被定义为免疫显性CTL表位，但我们之前报道过，肽段Melan-A/MART-1(26-35)能被大多数肿瘤反应性CTL克隆更有效地识别。如此处所示，黑色素瘤患者或健康个体的血液淋巴细胞在体外用肽段Melan-A/MART-1(26-35)刺激后产生的CTL群体可特异性杀伤HLA-A2+黑色素瘤抗原A+同种异体黑色素瘤细胞，因此表明它们在过继性免疫治疗中有潜在用途。我们对循环CTL前体（CTLp）的表面表型进行了特征分析，这些CTLp对体外用肽段Melan-A/MART-1(26-35)刺激有反应。在黑色素瘤患者中，这些CTLp主要表达CD45RO记忆标志物。相比之下，在健康个体中，它们主要（尽管不是唯一）存在于CD8 T细胞的CD45RA亚群中。转移性黑色素瘤HLA-A2+患者外周血淋巴细胞中黑色素瘤抗原A/MART-1特异性CTLp表达记忆表型的证明，为该抗原在肿瘤进展过程中可能发生体内启动提供了直接证据。
