Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1.
Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells chronically infected by human immunodeficiency virus type 1.
复制标题
DOI：
10.1084/jem.180.4.1283
复制
发表时间：
1994-10-01
期刊：
影响因子：
--
通讯作者：
Eisen HN
中科院分区：
文献类型：
--
作者：
Tsomides TJ;Aldovini A;Johnson RP;Walker BD;Young RA;Eisen HN
我们建立了几种稳定且均匀表达人类免疫缺陷病毒1型（HIV-1）的细胞系的长期培养，以便(a)鉴定由HIV-1血清阳性个体的细胞毒性T淋巴细胞（CTL）识别的自然处理的HIV-1肽，(b)考虑hiv感染细胞上自然发生的表位密度可能限制CTL裂解它们的假设。两种A2限制性CD8+ CTL特异性HIV-1 gag或逆转录酶（RT）识别感染细胞的三氟乙酸（TFA）提取物中的单个自然处理的HIV-1肽：gag 77-85 （SLYNTVATL）或RT 476-484 （ILKEPVHGV）。这两种加工的肽与合成的肽相匹配，这些合成肽在细胞毒性试验中具有最佳活性，并且具有a2相关肽所描述的一致基序。它们的丰度分别为每个感染Jurkat-A2细胞约400个和约12个分子。其他合成的在亚纳摩尔浓度下具有活性的HIV-1肽在感染细胞中不存在。除了抗原处理突变株T2外，受HIV感染的HLA-A2+细胞系均可被A2限制性CTL特异性裂解，尽管受感染的Jurkat-A2细胞被rt特异性CTL裂解的效果比gag特异性CTL更差，这表明天然肽的低细胞表面密度可能会限制某些HIV特异性CTL的有效性，尽管它们对合成肽处理的靶细胞具有强烈的活性。
We have established long-term cultures of several cell lines stably and uniformly expressing human immunodeficiency virus type 1 (HIV-1) in order to (a) identify naturally processed HIV-1 peptides recognized by cytotoxic T lymphocytes (CTL) from HIV-1-seropositive individuals and (b) consider the hypothesis that naturally occurring epitope densities on HIV-infected cells may limit their lysis by CTL. Each of two A2- restricted CD8+ CTL specific for HIV-1 gag or reverse transcriptase (RT) recognized a single naturally processed HIV-1 peptide in trifluoroacetic acid (TFA) extracts of infected cells: gag 77-85 (SLYNTVATL) or RT 476-484 (ILKEPVHGV). Both processed peptides match the synthetic peptides that are optimally active in cytotoxicity assays and have the consensus motif described for A2-associated peptides. Their abundances were approximately 400 and approximately 12 molecules per infected Jurkat-A2 cell, respectively. Other synthetic HIV-1 peptides active at subnanomolar concentrations were not present in infected cells. Except for the antigen processing mutant line T2, HIV- infected HLA-A2+ cell lines were specifically lysed by both A2- restricted CTL, although infected Jurkat-A2 cells were lysed more poorly by RT-specific CTL than by gag-specific CTL, suggesting that low cell surface density of a natural peptide may limit the effectiveness of some HIV-specific CTL despite their vigorous activity against synthetic peptide-treated target cells.