Cross-reactive cytotoxic T lymphocytes against a HIV-1 p24 epitope in slow progressors with B*57
Cross-reactive cytotoxic T lymphocytes against a HIV-1 p24 epitope in slow progressors with B*57
复制标题
DOI：
10.1097/00002030-200205030-00002
复制
发表时间：
2002-05-03
期刊：
影响因子：
3.8
通讯作者：
Rowland-Jones, SL
中科院分区：
文献类型：
--
作者：
Gillespie, GMA;Kaul, R;Rowland-Jones, SL
目的：为了确定来自表达B*5701和B*5703的HIV-1感染患者的CD 8 T淋巴细胞是否对保守的p24表位的不同变体显示出广泛的交叉反应性，这可能解释具有HLA-B * 57的HIV-1感染个体的良好预后。设计：从肯尼亚的内罗毕和英国的牛津招募B*5701+和B*5703+。所有患者HIV阳性至少8年，可以归类为缓慢progressers.Methods：CD 8细胞毒性T细胞克隆产生的B*5701+和B*5703+捐助者和测试他们的能力，以识别进化枝变异的索引p24表位在标准的细胞溶解试验。在新鲜分离的外周血单核细胞（PBMC）的交叉反应进行了评估，干扰素-γ（IFN γ）的生产和tetramer binding.Results：广泛的交叉反应，细胞溶解和tetramer结合观察到在CD 8 T细胞克隆的患者窝藏的索引表位序列。在新鲜分离的PBMC中，交叉反应模式相似，但个体之间在产生的反应强度和呼吸方面存在差异。一种常见的变体诱导了与四聚体结合的不寻常反应，但通常不能诱导IFN γ产生，另一种是IFN γ和细胞溶解活性的弱刺激物。B*5701+和B5703+供体对显性p24表位的常见和罕见变体表现出广泛的功能交叉反应性，这可能与B*57等位基因与缓慢进展为AIDS相关。(C)2002年利平科特威廉姆斯威尔金斯。
Objectives: To determine whether CD8 T lymphocytes from HIV-1-infected patients expressing B*5701 and B*5703 show broad cross-reactivity against different variants of a conserved p24 epitope, which might account for the good prognosis of HIV-1-infected individuals with HLA-B*57.Design: B*5701+ and B*5703+ were recruited from Nairobi, Kenya and from Oxford, UK. All patients had been HIV positive for at least 8 years and could be categorized as slow progressors.Methods: CD8 cytotoxic T cell clones were generated from B*5701+ and B*5703+ donors and tested for their ability to recognize clade variants of an index p24 epitope in standard cytolytic assays. Cross-reactive responses in freshly isolated peripheral blood mononuclear cells (PBMC) were assessed by interferon-gamma (IFNgamma) production and tetramer binding.Results: Broad cross-clade reactivity for both cytolysis and tetramer binding was observed in CD8 T cell clones from patients harbouring the index epitope sequence. Patterns of cross-reactivity were similar in freshly isolated PBMC but varied between individuals in terms of strength and breath of responses generated. One common variant induced an unusual response with tetramer binding but often failed to induce IFNgamma production, and another was a weak stimulator of both IFNgamma and cytolytic activity.Conclusion: B*5701+ and B5703+ donors demonstrate broad functional cross-reactivity to both common and rare variants of a dominant p24 epitope, which could be relevant to the association of B*57 alleles with slow progression to AIDS. (C) 2002 Lippincott Williams Wilkins.