SPECIFIC, MAJOR HISTOCOMPATIBILITY COMPLEX - UNRESTRICTED RECOGNITION OF TUMOR-ASSOCIATED MUCINS BY HUMAN CYTO-TOXIC T-CELLS
SPECIFIC, MAJOR HISTOCOMPATIBILITY COMPLEX - UNRESTRICTED RECOGNITION OF TUMOR-ASSOCIATED MUCINS BY HUMAN CYTO-TOXIC T-CELLS
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DOI：
10.1073/pnas.86.18.7159
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发表时间：
1989-09-01
影响因子：
11.1
通讯作者：
FINN, OJ
中科院分区：
文献类型：
--
作者：
BARND, DL;LAN, MS;FINN, OJ
我们以前曾报道过建立细胞毒性T细胞系，从胰腺癌患者，通过不断刺激肿瘤引流淋巴结细胞与同种异体胰腺肿瘤细胞系。在对其表型和肿瘤特异性进行初步表征后，对其中一种细胞系W.D.进行了详细研究，表明它识别一种特异性抗原，一种在胰腺和乳腺肿瘤以及肿瘤细胞系上表达的大的且高度糖基化的粘蛋白分子。尽管这种识别表现为主要组织相容性复合体（MHC）不受限制，但细胞毒性T细胞使用的抗原受体是α/。β的异二聚体，通常在MHC限制性T细胞上发现。然而，靶抗原是非典型的，其在自身MHC不存在的情况下直接结合和激活T细胞的能力，推测是通过丰富和规律重复的抗原表位。这些发现很重要，因为它们证明了针对人类肿瘤相关抗原的特异性T细胞应答。除了胰腺和乳腺肿瘤外，已知各种粘蛋白分子由上皮细胞来源的其他肿瘤产生，并且可以预期刺激类似的T细胞介导的免疫应答。
We have previously reported the establishment of cytotoxic T-cell lines, from pancreatic cancer patients, by continuously stimulating tumor-drainage lymph node cells with allogeneic pancreatic tumor cell lines. After the preliminary characterization of their phenotype and tumor specificity, detailed studies performed with one of the cell lines, W.D., show that it recognizes a specific antigen, a large and heavily glycosylated mucin molecule, expressed on pancreatic and breast tumors and tumor cell lines. Although this recognition appers major histocompatibility complex (MHC)-unrestricted, the antigen receptor used by the cytotoxic T cell is the .alpha./.beta. heterodimer, typically found on MHC-restricted T cells. The target antigen is atypical, however, in its ability to directly bind and activate the T cells in the absence of self MHC, presumbly by abundant and regularly repeated antigenic epitopes. These findings are important because they demonstrate a specific T-cell response against a human tumor-associated antigen. In addition to pancreatic and breast tumors, various mucin molecules are known to be produced by other tumors of epithelial cell origin and could be expected to stimulate similar T-cell-mediated immune responses.