Characterization of an HLA-C-restricted CTL response in chronic HIV infection
Characterization of an HLA-C-restricted CTL response in chronic HIV infection
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DOI：
10.1002/eji.200939634
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发表时间：
2010-04-01
影响因子：
5.4
通讯作者：
Rowland-Jones, Sarah L.
中科院分区：
文献类型：
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作者：
Makadzange, Azure T.;Gillespie, Geraldine;Rowland-Jones, Sarah L.
HIV特异性CTL在宿主控制HIV感染中起重要作用。HIV-nef可能通过选择性下调HLA-A和HLA-B分子的表达而促进HIV感染细胞逃避CTL识别，而HLA-C的表面表达不受影响。HLA-C限制性CTL应答以前在很大程度上被忽视，特征也很差。我们检测了10名携带HLA-Cw 04等位基因的未接受过抗逆转录病毒治疗的白人和非洲慢性HIV-1感染者（至少8年; CD 4细胞计数在50-350范围内）的HLA-C限制性CTL的频率、功能和表型。使用IFN-γ ELISPOT测定分析识别HIV-1包膜内保守表位（aa 375-383 SF 9）的HLA-Cw 04限制性CTL，并通过流式细胞术进行表型分析。HLA-C限制性CTL在HIV特异性免疫应答中起重要作用，可占总免疫应答的54%。HLA-C限制性CTL在功能和表型上与HLA-A和HLA-B限制性CTL相同。慢性HIV感染中的HLA-C限制性CTL是具有中间表型的记忆细胞，其特征在于高CD 27和低CD 28表达以及缺乏穿孔素产生。
HIV-specific CTL play an important role in the host control of HIV infection. HIV-nef may facilitate escape of HIV-infected cells from CTL recognition by selectively downregulating the expression of HLA-A and HLA-B molecules, while surface expression of HLA-C is unaffected. The HLA-C-restricted CTL responses have previously been largely ignored and poorly characterized. We examined the frequency, function, and phenotype of HLA-C-restricted CTL in ten antiretroviral therapy-naive Caucasian and African individuals with chronic HIV-1 infection (for at least 8 years; CD4 cell counts in the range of 50-350) who carried the HLA-Cw04 allele. HLA-Cw04-restricted CTL that recognize a conserved epitope within HIV-1 envelope (aa 375-383 SF9) were analyzed using IFN-gamma ELISPOT assays and phenotypic analysis was carried out by flow cytometry. HLA-C-restricted CTL play an important role in the HIV-specific response, and can account for as much as 54% of the total response. HLA-C-restricted CTL are functionally and phenotypically identical to HLA-A- and HLA-B-restricted CTL. HLA-C-restricted CTL in chronic HIV infection are memory cells of an intermediate phenotype, characterized by high CD27 and low CD28 expression and lack of perforin production.