CD8-independent tumor cell recognition is a property of the T cell receptor and not the T cell
CD8-independent tumor cell recognition is a property of the T cell receptor and not the T cell
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DOI：
10.4049/jimmunol.170.5.2582
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发表时间：
2003-03-01
影响因子：
4.4
通讯作者：
Nishimura, MI
中科院分区：
文献类型：
--
作者：
Roszkowski, JJ;Yu, DC;Nishimura, MI
CD 8辅助受体通过稳定TCR/肽/MHC复合物和/或通过与细胞内激酶Lck和LAT相互作用增加T细胞亲合力来增强T细胞功能。我们以前报道了一种CD 4（+）T细胞（TIL 13831），它识别肿瘤相关的Ag酪氨酸酶在HLA-A2的背景下。为了确定CD 8非依赖性肿瘤细胞识别是否是TCR的特性，我们使用逆转录病毒转导在CD 8（-）鼠淋巴瘤58 α（-）/β（-）中表达TIL 13831 TCR。用人TCR V β亚家族特异性抗体和小鼠CD 3特异性抗体对TCR转导的细胞进行免疫荧光染色，证实了转移的TCR的表面表达和小鼠CD 3的共表达。与单独的T2细胞或HLA-A2（-）黑素瘤细胞相比，转导的效应细胞在酪氨酸酶肽脉冲的T2细胞的Ag呈递以及HLA-A2（+）黑素瘤细胞系的刺激下分泌显著量的IL-2。TCR转导的克隆的进一步分析证明了T细胞亲合力和TCR的细胞表面表达之间的相关性。因此，TIL 13831 TCR具有足够的亲和力以在不存在CD 8表达的情况下介导对由肿瘤细胞表达的生理水平的Ag的识别。
The CD8 coreceptor enhances T cell function by stabilizing the TCR/peptide/MHC complex and/or increasing T cell avidity via interactions with the intracellular kinases Lck and LAT. We previously reported a CD4(+) T cell (TIL 13831), which recognizes the tumor-associated Ag tyrosinase in the context of HLA-A2. To determine Whether CD8 independent tumor cell recognition is a property of the TCR, we used retroviral transduction to express the TIL 13831 TCR in the CD8(-) murine lymphoma, 58 alpha(-)/beta(-). Immunofluorescent staining of TCR-transduced cells with human TCR Vbeta subfamily-specific and mouse CD3-specific Abs confirmed surface expression of the transferred TCR and coexpression of mouse CD3. Transduced effector cells secreted significant amounts of IL-2 following Ag presentation by tyrosinase peptide-pulsed T2 cells as well as stimulation with HLA-A2(+) melanoma lines compared with T2 cells alone or HLA-A2(-) melanoma cells. Further analysis of TCR-transduced clones demonstrated a correlation between T cell avidity and cell surface expression of the TCR. Therefore, the TIL 13831 TCR has sufficient affinity to mediate recognition of the physiologic levels of Ag expressed by tumor cells in the absence of CD8 expression.