Efficient identification of novel HLA-A(*)0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis.
Efficient identification of novel HLA-A(*)0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis.
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DOI：
10.1084/jem.193.1.73
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Melief CJ
中科院分区：
文献类型：
--
作者：
Kessler JH;Beekman NJ;Bres-Vloemans SA;Verdijk P;van Veelen PA;Kloosterman-Joosten AM;Vissers DC;ten Bosch GJ;Kester MG;Sijts A;Wouter Drijfhout J;Ossendorp F;Offringa R;Melief CJ
我们报道了使用改进的“反向免疫学”策略有效鉴定肿瘤相关抗原PRAME中四个人类组织相容性白细胞抗原(HLA)-A*0201呈递的细胞毒性T淋巴细胞（CTL）表位。除了基于基序的HLA-A*0201结合预测和实际结合及稳定性分析之外，在表位预测过程中还包括了蛋白酶体介导的包含候选表位的多肽的体外消化分析。蛋白酶体切割模式分析，特别是确定假设表位的正确cooh末端切割，允许更准确和选择性地预测CTL表位。在19个高亲和力的HLA-A*0201结合肽中，只有4个（21%）是由蛋白酶体在体外有效生成的。这种方法避免了对未处理的高亲和力结合肽的费力的CTL反应诱导，并限制了要检测的结合肽的数量。4个鉴定的表位（VLDGLDVLL, PRA100-108； SLYSFPEPEA, PRA142-151； ALYVDSLFFL, PRA300-309； SLLQHLIGL, PRA425-433）诱导的CTL克隆可裂解表达PRAME和HLA-A*0201的黑色素瘤、肾癌、肺癌和乳腺癌细胞系。这表明这些表位在不同组织学来源的癌细胞上表达，使它们成为癌症免疫治疗的有吸引力的靶点。
We report the efficient identification of four human histocompatibility leukocyte antigen (HLA)-A*0201–presented cytotoxic T lymphocyte (CTL) epitopes in the tumor-associated antigen PRAME using an improved “reverse immunology” strategy. Next to motif-based HLA-A*0201 binding prediction and actual binding and stability assays, analysis of in vitro proteasome-mediated digestions of polypeptides encompassing candidate epitopes was incorporated in the epitope prediction procedure. Proteasome cleavage pattern analysis, in particular determination of correct COOH-terminal cleavage of the putative epitope, allows a far more accurate and selective prediction of CTL epitopes. Only 4 of 19 high affinity HLA-A*0201 binding peptides (21%) were found to be efficiently generated by the proteasome in vitro. This approach avoids laborious CTL response inductions against high affinity binding peptides that are not processed and limits the number of peptides to be assayed for binding. CTL clones induced against the four identified epitopes (VLDGLDVLL, PRA100–108; SLYSFPEPEA, PRA142–151; ALYVDSLFFL, PRA300–309; and SLLQHLIGL, PRA425–433) lysed melanoma, renal cell carcinoma, lung carcinoma, and mammary carcinoma cell lines expressing PRAME and HLA-A*0201. This indicates that these epitopes are expressed on cancer cells of diverse histologic origin, making them attractive targets for immunotherapy of cancer.
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DOI：
10.1084/jem.179.3.1005
发表时间：
1994-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bakker AB;Schreurs MW;de Boer AJ;Kawakami Y;Rosenberg SA;Adema GJ;Figdor CG
通讯作者：
Figdor CG
影响因子：
4.8
作者：
Beninga, J;Rock, KL;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
3.2
作者：
Herman, J;vanderBruggen, P;Coulie, PG
通讯作者：
Coulie, PG
影响因子：
32.4
作者：
BOEL, P;WILDMANN, C;VANDERBRUGGEN, P
通讯作者：
VANDERBRUGGEN, P
DOI：
10.1084/jem.178.2.489
发表时间：
1993-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brichard V;Van Pel A;Wölfel T;Wölfel C;De Plaen E;Lethé B;Coulie P;Boon T
通讯作者：
Boon T