DIFFERENCES IN THE ANTIGENS RECOGNIZED BY CYTOLYTIC T-CELLS ON 2 SUCCESSIVE METASTASES OF A MELANOMA PATIENT ARE CONSISTENT WITH IMMUNE SELECTION

DIFFERENCES IN THE ANTIGENS RECOGNIZED BY CYTOLYTIC T-CELLS ON 2 SUCCESSIVE METASTASES OF A MELANOMA PATIENT ARE CONSISTENT WITH IMMUNE SELECTION
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DOI:
10.1002/eji.1830250206
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发表时间:
1995-02-01
影响因子:
5.4
通讯作者:
COULIE, PG
COULIE, PG
中科院分区:
医学3区
文献类型:
--
作者:
LEHMANN, F;MARCHAND, M;COULIE, PG

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我们研究了两个黑素瘤细胞系上的自体溶细胞性T淋巴细胞(CTL)识别的抗原模式,这两个黑素瘤细胞系来自于几年前从患者LB 33身上切除的转移瘤。细胞系LB 33-MEL. A在1988年手术后获得。用1990年从该患者收集的血淋巴细胞获得了大量针对LB 33-MEL. A的CTL克隆。对这些CTL克隆具有抗性的黑素瘤细胞的体外选择表明,自体CTL在LB 33-MEL. A上识别至少五种不同的抗原。其中4种抗原分别由HLA-A28、B13、B44和Cw 6提呈。该患者一直保持无病状态,直到1993年检测到转移并用于获得细胞系LB 33-MEL. B。该细胞系证明对所有针对LB 33-MEL. A细胞的CTL克隆的裂解具有抗性,并且除了HLA-A24之外不显示HLA I类分子的表达。使用LB 33-MEL.B细胞刺激1994年从患者收集的血液淋巴细胞,我们获得了裂解这些细胞的CTL克隆。所有这些CTL克隆识别HLA-A24提呈的新抗原。这些结果表明,在患者LB 33中,黑素瘤细胞可能在抗肿瘤CTL应答的选择性压力下失去了几种HLA分子的表达。
We have studied the patterns of antigens recognized by autologous cytolytic T lymphocytes (CTL) on two melanoma cell lines derived from metastases that were removed from patient LB33 at several years distance. Cell line LB33-MEL.A was obtained after surgery in 1988. A large number of CTL clones directed against LB33-MEL.A was obtained with blood lymphocytes collected from the patient in 1990. In vitro selection of melanoma cells that were resistant to these CTL clones indicated that al least five different antigens were recognized on LB33-MEL.A by autologous CTL. Four of these antigens were found to be presented by HLA-A28, B13, B44 and Cw6, respectively. The patient remained disease-free until 1993 when a metastasis was detected and was used to obtain cell line LB33-MEL.B. This cell line proved resistant to lysis by all the CTL clones directed against the LB33-MEL.A cells and showed no expression of HLA class I molecules except for HLA-A24. Using LB33-MEL.B cells to stimulate blood lymphocytes collected from the patient in 1994 we derived CTL clones that lysed these cells. All these CTL clones recognized a new antigen presented by HLA-A24. These results suggest that in patient LB33 the melanoma cells may have lost the expression of several HLA molecules under the selective pressure of an anti-tumor CTL response.