Natural T-HELPER immunity against human papillomavirus type 16 (HPV16) E7-derived peptide epitopes in patients with HPV16-positive cervical lesions: Identification of 3 human leukocyte antigen class II-restricted epitopes
Natural T-HELPER immunity against human papillomavirus type 16 (HPV16) E7-derived peptide epitopes in patients with HPV16-positive cervical lesions: Identification of 3 human leukocyte antigen class II-restricted epitopes
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DOI：
10.1002/1097-0215(200002)9999:9999
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发表时间：
2001-03-01
影响因子：
6.4
通讯作者：
Offringa, R
中科院分区：
文献类型：
--
作者：
van der Burg, SH;Ressing, ME;Offringa, R
肿瘤特异性辅助性T细胞（Th）免疫在天然和疫苗诱导的肿瘤免疫防御中起着关键作用。由于大多数宫颈癌表达人乳头瘤病毒16型（HPV16）E7癌蛋白，因此详细研究Th对该靶抗原的反应是很重要的。通过从HLA分型的健康供体的PBMC培养，我们鉴定了HPV 16 E7（E7（41 - 72））的中心部分为该抗原内的主要免疫原性区域。此外，我们在该区域内定位了3个不同的Th表位（DR15/E7（50 - 62）、DR3/E7（43 - 77）、DQ 2/E7（35 - 50））。在一个平行的方法中，采用IFN-γ ELISPOT分析，我们检测了HPV16（+）病变受试者中针对HPV16 E7的Th免疫。这些应答中有几个与我们研究中定义的3 Th表位相匹配。许多其他HPV16（+）受试者没有显示任何E7特异性I型产丝氨酸T细胞免疫，表明免疫应答失败。我们的综合数据表明，使用所述ELISPOT测定法对HPV 16特异性T细胞免疫进行更广泛和纵向分析，以及对HPV+病变个体进行HPV特异性疫苗接种。(C)2001 Wiley-Liss，Inc.
Tumor-specific T-helper (Th) immunity was found to play a pivotal role in the natural and vaccine-induced immune defense against tumors. Since the majority of cervical cancers express human papillomavirus type 16 (HPV16) E7 oncoprotein, it is important to investigate the Th response against this target antigen in detail. By means of PBMC cultures from HLA-typed healthy donors, we identified the central part of HPV16 E7 (E7(41-72)) as the major immuno-genic region within this antigen. Furthermore, we mapped 3 distinct Th epitopes within this region (DR15/E7(50-62), DR3/E7(43-77) DQ2/E7(35-50)). In a parallel approach, employing IFN-gamma ELISPOT analysis, we detected Th immunity against HPV16 E7 in subjects with HPV16(+) lesions. Several of these responses matched with the 3 Th epitopes defined in our study, A number of other HPV16(+) subjects did not display any E7-specific type I cytokine-producing T-cell immunity, indicating failure of the immune response. Our combined data argue for more extensive as well as longitudinal analysis of HPV16-specific T-cell immunity using the ELISPOT assay described, as well as for HPV-specific vaccination of individuals with HPV+ lesions. (C) 2001 Wiley-Liss, Inc.