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参与γ/δ细胞毒性T淋巴细胞与伯基特淋巴瘤相互作用的新型肿瘤相关辅助分子。

Novel tumor-associated accessory molecules involved in the gamma/delta cytotoxic T-lymphocyte-Burkitt's lymphoma interaction.

作者信息

Nelson E L, Kim H T, Mar N D, Goralski T J, McIntyre B W, Clayberger C, Krensky A M

机构信息

Department of Medicine, Stanford University School of Medicine, CA 94305.

出版信息

Cancer. 1995 Feb 1;75(3):886-93. doi: 10.1002/1097-0142(19950201)75:3<886::aid-cncr2820750321>3.0.co;2-g.

Abstract

BACKGROUND

Tumor specific cytotoxic T lymphocytes (CTL) recognize antigen via the T-cell receptor (TCR). In addition, recognition requires accessory molecules involved in adhesion and signal transduction. The authors previously have characterized an autologous, Burkitt's lymphoma specific CTL line that uses the gamma-delta TCR to recognize antigen in a nonclassical context. The current study was undertaken to identify novel accessory molecules involved in this unusual TCR-tumor cell interaction.

METHODS

A panel of monoclonal antibodies was generated against a Burkitt's lymphoma cell line and was screened for inhibition of autologous, tumor specific, cytolysis by a gamma-delta CTL line. Proteins identified by these monoclonal antibodies were further characterized by fluorescent-activated cell sorter analysis, Western blot and immunoprecipitation.

RESULTS

Three known (CD5, CD43, and CD11a/CD18) and three novel (BAM-1, BAM-2, and BAM-3) cell surface molecules involved in the gamma-delta CTL-Burkitt's lymphoma interaction were identified and characterized.

CONCLUSIONS

This study identifies and provides a preliminary characterization of three novel Burkitt's lymphoma-associated molecules involved in the gamma-delta CTL-tumor cell interaction and demonstrates that CD5, CD43, and CD11a/CD18 are involved in this interaction. It is likely that other unidentified accessory molecules are also involved in this and other effector cell-tumor interactions. Identification of such molecules may be useful in the design of new immunotherapeutic approaches.

摘要

背景

肿瘤特异性细胞毒性T淋巴细胞(CTL)通过T细胞受体(TCR)识别抗原。此外,识别还需要参与黏附和信号转导的辅助分子。作者之前已鉴定出一种自体的、伯基特淋巴瘤特异性CTL系,该CTL系利用γδTCR在非经典环境中识别抗原。当前研究旨在鉴定参与这种不寻常的TCR-肿瘤细胞相互作用的新型辅助分子。

方法

制备了一组针对伯基特淋巴瘤细胞系的单克隆抗体,并筛选其对γδCTL系介导的自体肿瘤特异性细胞溶解的抑制作用。通过荧光激活细胞分选分析、蛋白质印迹和免疫沉淀进一步鉴定这些单克隆抗体识别的蛋白质。

结果

鉴定并表征了三种已知的(CD5、CD43和CD11a/CD18)以及三种新型的(BAM-1、BAM-2和BAM-3)参与γδCTL-伯基特淋巴瘤相互作用的细胞表面分子。

结论

本研究鉴定并初步表征了三种参与γδCTL-肿瘤细胞相互作用的新型伯基特淋巴瘤相关分子,并证明CD5、CD43和CD11a/CD18参与了这种相互作用。很可能还有其他未鉴定的辅助分子也参与了这种以及其他效应细胞-肿瘤相互作用。鉴定此类分子可能有助于设计新的免疫治疗方法。

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