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HLA-A2限制性CTL系及黑色素瘤患者抗体对gp43肿瘤相关抗原肽的识别。

Recognition of gp43 tumor-associated antigen peptide by both HLA-A2 restricted CTL lines and antibodies from melanoma patients.

作者信息

Takahashi T, Irie R F, Morton D L, Hoon D S

机构信息

Department of Biotechnology Sciences, John Wayne Cancer Institute, Santa Monica, California 90404, USA.

出版信息

Cell Immunol. 1997 Jun 15;178(2):162-71. doi: 10.1006/cimm.1997.1126.

DOI:10.1006/cimm.1997.1126
PMID:9225007
Abstract

Previously, we detected a 43-kDa tumor-associated antigen (TAA) using the human monoclonal antibody L92, which recognizes the tetramer peptide KYQI. In the present study, cell lines of cytotoxic T lymphocytes (CTL) specific to the gp43 peptide (DLTMKYQIF) were established from peripheral blood lymphocytes (PBL) of melanoma patients. Patients' PBL (n = 326) of different HLA Class I types were assessed for gp43 CTL activity. CTL specific to gp43 peptide were generated only from HLA-A2 melanoma patients and not normal donors. gp43 CTL recognized gp43 peptide-pulsed autologous BLC and T2 HLA-A2 target cell lines. Furthermore, CTL lines were shown to kill both HLA-A2 autologous and HLA-A2 allogeneic melanoma cell lines, indicating that gp43 peptide can be processed endogenously and presented by melanoma cells as a common TAA. The gp43 CTL lines did not kill normal cells. Specific amino acids of the peptide were shown to be important determinants in stimulation and recognition of CTL. gp43 peptide, recognized by both antibodies and T cells of melanoma patients, is a novel TAA peptide that may play an important role in anti-tumor immunity in human.

摘要

此前,我们使用人源单克隆抗体L92检测到一种43 kDa的肿瘤相关抗原(TAA),该抗体可识别四聚体肽KYQI。在本研究中,从黑色素瘤患者的外周血淋巴细胞(PBL)中建立了对gp43肽(DLTMKYQIF)特异的细胞毒性T淋巴细胞(CTL)细胞系。评估了不同HLA I类类型患者的PBL(n = 326)的gp43 CTL活性。仅从HLA - A2黑色素瘤患者而非正常供体中产生了对gp43肽特异的CTL。gp43 CTL识别gp43肽脉冲处理的自体BLC和T2 HLA - A2靶细胞系。此外,CTL系显示可杀死HLA - A2自体和HLA - A2同种异体黑色素瘤细胞系,表明gp43肽可在内源性加工后由黑色素瘤细胞作为共同TAA呈递。gp43 CTL系不杀伤正常细胞。该肽的特定氨基酸被证明是CTL刺激和识别的重要决定因素。gp43肽可被黑色素瘤患者的抗体和T细胞识别,是一种新型TAA肽,可能在人类抗肿瘤免疫中发挥重要作用。

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引用本文的文献

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Br J Cancer. 1999 Sep;81(2):342-9. doi: 10.1038/sj.bjc.6690698.
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Augmentation of IgM antibody to gp43 tumor-associated antigen peptide by melanoma cell vaccine.黑色素瘤细胞疫苗增强针对gp43肿瘤相关抗原肽的IgM抗体
J Clin Immunol. 1998 Jul;18(4):299-305. doi: 10.1023/a:1027342024618.