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首页> 外文期刊>Journal of immunotherapy >Melanoma-Reactive CD8+ T cells recognize a novel tumor antigen expressed in a wide variety of tumor types.
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Melanoma-Reactive CD8+ T cells recognize a novel tumor antigen expressed in a wide variety of tumor types.

机译：黑色素瘤反应性CD8 + T细胞可识别在多种肿瘤类型中表达的新型肿瘤抗原。

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An autologous melanoma cell line selected for loss of expression of the immunodominant MART-1 and gp100 antigens was initially used to carry out a mixed lymphocyte tumor culture (MLTC) in a patient who expressed the human leukocyte antigen (HLA)-AI and HLA-A2 class I major histocompatibility complex alleles. Ten clones identified from this MLTC seemed to recognize melanoma in an HLA-A1-restricted manner but failed to recognize a panel of previously described melanoma antigens. The screening of an autologous melanoma cDNA library with one HLA-Al-restricted melanoma-reactive T-cell clone resulted in the isolation of a cDNA clone called AIM-2 (antigen isolated from immunoselected melanoma-2). The AIM-2 transcript seemed to have retained an intronic sequence based on its alignment with genomic sequences as well as expressed sequence tags. This transcript was not readily detected after Northern blot analysis of melanoma mRNA, indicating that only low levels of this product may be expressed in tumor cells. Quantitative reverse transcriptase-polymerase chain reaction analysis, however, demonstrated a correlation between T-cell recognition and expression in HLA-A1-expressing tumor cell lines. A peptide that was encoded within a short open reading frame of 23 amino acids and conformed to the HLA-A1 binding motif RSDSGQQARY was found to represent the T-cell epitope. The AIM-2-reactive T-cell clone recognized a number of neuroectodermal tumors as well as breast, ovarian, and colon carcinomas that expressed HLA-A1, indicating that this represents a widely expressed tumor antigen. Thus, AIM-2 may represent a potential target for the development of vaccines in patients bearing tumors of a variety of histologies.
机译：为表达免疫白细胞抗原（MART-1）和gp100抗原的表达而选择的自体黑素瘤细胞系最初用于表达人白细胞抗原（HLA）-AI和HLA-的患者的混合淋巴细胞肿瘤培养（MLTC） A2类主要组织相容性复杂等位基因。从此MLTC鉴定出的十个克隆似乎以HLA-A1限制性方式识别黑色素瘤，但未能识别一组先前描述的黑色素瘤抗原。用一个HLA-A1限制性黑素瘤反应性T细胞克隆筛选自体黑素瘤cDNA文库，导致分离出一种称为AIM-2的cDNA克隆（从免疫选择的黑素瘤2中分离的抗原）。基于与基因组序列以及表达的序列标签的比对，AIM-2转录本似乎保留了一个内含子序列。在对黑色素瘤mRNA进行Northern印迹分析后，该转录本不容易被检测到，表明该产物仅在肿瘤细胞中表达低水平。定量逆转录酶-聚合酶链反应分析，但是，表明T细胞识别和表达HLA-A1的肿瘤细胞系中表达之间的相关性。发现在23个氨基酸的短开放阅读框中编码并符合HLA-A1结合基序RSDSGQQARY的肽代表T细胞表位。 AIM-2反应性T细胞克隆可识别许多表达HLA-A1的神经外胚层肿瘤以及乳腺癌，卵巢癌和结肠癌，这表明它代表了广泛表达的肿瘤抗原。因此，AIM-2可能代表了携带多种组织学肿瘤的患者开发疫苗的潜在目标。

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