Detection and induction of CTLs specific for SYT-SSX-derived peptides in HLA-A24+ patients with synovial sarcoma
Detection and induction of CTLs specific for SYT-SSX-derived peptides in HLA-A24+ patients with synovial sarcoma
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DOI：
10.4049/jimmunol.169.3.1611
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发表时间：
2002-08-01
影响因子：
4.4
通讯作者：
Sato, N
中科院分区：
文献类型：
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作者：
Sato, Y;Nabeta, Y;Sato, N
为了研究滑膜肉瘤特异性SYT-SSX融合基因衍生的肽的免疫原性，我们根据HLA-A24的结合基序合成了四种肽。其中，SS391 （PYGYDQIMPK）和SS393 （GYD QIMPKK）来源于SYT-SSX的断点，SS449a （AWTHRLRER）和SS449b （AWTHRLRERK）来源于SSX区。在16例滑膜肉瘤患者中使用HLA-A24/SYT-SSX肽四聚体检测这些肽与CTL前体（CTLps）的反应性，并从4例HLA-A24（+）滑膜肉瘤患者中诱导特异性CTL。四聚体分析显示，CTLp对SYT-SSX的频率增加与滑膜肉瘤患者肺转移有关（p < 0.03）。利用SS391和SS393的肽混合物，以HLA- i类限制的方式裂解表达SYT-SSX的HLA- a24（+）滑膜肉瘤细胞以及肽脉冲靶细胞，从两例滑膜肉瘤患者的PBLs诱导ctl。这些发现表明，SYT-SSX基因产物的异常表达在体内引发了SYT-SSX特异性的CTLps，并增加了其在滑膜肉瘤患者中的频率。SYT-SSX肽的鉴定可能为HLA-A24（+）滑膜肉瘤患者设计基于肽的免疫治疗方法提供机会。
To investigate the immunogenic property of peptides derived from the synovial sarcoma-specific SYT-SSX fusion gene, we synthesized four peptides according to the binding motif for HLA-A24. The peptides, SS391 (PYGYDQIMPK) and SS393 (GYD QIMPKK), were derived from the breakpoint of SYT-SSX, and SS449a (AWTHRLRER) and SS449b (AWTHRLRERK) were from the SSX region. These peptides were tested for their reactivity with CTL precursors (CTLps) in 16 synovial sarcoma patients using HLA-A24/SYT-SSX peptide tetramers and also for induction of specific CTLs from four HLA-A24(+) synovial sarcoma patients. Tetramer analysis indicated that the increased CTLp frequency to the SYT-SSX was associated with pulmonary metastasis in synovial sarcoma patients (p < 0.03). CTLs were induced from PBLs of two synovial sarcoma patients using the peptide mixture of SS391 and SS393, which lysed HLA-A24(+) synovial sarcoma cells expressing SYT-SSX as well as the peptide-pulsed target cells in an HLA class I-restricted manner. These findings suggest that aberrantly expressed SYT-SSX gene products have primed SYT-SSX-specific CTLps in vivo and increased their frequency in synovial sarcoma patients. The identification of SYT-SSX peptides may offer an opportunity to design peptide-based immunotherapeutic approaches for HLA-A24(+) patients with synovial sarcoma.