A rapid method to identify cytotoxic T-lymphocyte peptide epitopes from HLA-A2 (+) donors

A rapid method to identify cytotoxic T-lymphocyte peptide epitopes from HLA-A2 (+) donors
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DOI:
10.1016/s1040-8428(01)00112-3
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发表时间:
2001-07-01
影响因子:
6.2
通讯作者:
Hayes, RL
Hayes, RL
中科院分区:
医学2区
文献类型:
--
作者:
Castellanos, MR;Weinstein, G;Hayes, RL

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这将是有用的,开发一种方法来快速鉴定肽表位的疫苗开发。我们提出了一种算法,可以预测具有高结合活性的HLA-A2的序列。这些序列能够从人外周血淋巴细胞(PBMC)诱导特异性溶细胞细胞。根据锚定氨基酸组合,构建了一种计算机辅助算法来预测HLA-A2的结合活性。使用人乳头瘤病毒(HPV)18型E7癌蛋白来测试该算法。合成预测结合的肽,并通过使用T2细胞测定法测定结合活性。用HPV-18肽脉冲的T2细胞与PBMC孵育。进行细胞毒性试验。从110个可能的序列中,发现四个肽具有高结合活性。这些肽中的一种能够诱导显著的裂解。使用该选择过程,仅合成了可能序列总数的3.6%以鉴定免疫原性肽。我们的算法与T2结合试验允许一种快速的方法来检测肽表位。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
It would be useful to develop a method to rapidly identify peptide epitopes for vaccine development. We present an algorithm that can predict sequences that have a high binding activity for HLA-A2. These sequences were able to induce specific cytolytic cells from human peripheral blood lymphocytes (PBMC). A computer-assisted algorithm was constructed to predict binding activity for HLA-A2, according to anchoring amino acid combinations. The human papillomavirus (HPV) type 18 E7 oncoprotein was used to test the algorithm. Peptides predicted to bind were synthesized and binding activity was determined by using the T2 cell assay. T2 cells pulsed with HPV-18 peptides were incubated with PBMC. Cytotoxicity assays were performed. From 110 possible sequences, four peptides were found to have a high binding activity. One of these peptides was able to induce significant lysis. Using this selection process only 3.6% of the total number of possible sequences was synthesized to identify an immunogenic peptide. Our algorithm with the T2 binding assay allows a rapid method to detect peptide epitopes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.