Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA.
Nat Genet. 2009 Dec;41(12):1290-4. doi: 10.1038/ng.486.
A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells.
先前有研究表明，HLA-C 基因上游的一个 35kb 变异（-35C/T）与 HLA-C mRNA 表达水平和 HIV 病毒载量有关。我们对 1698 名欧洲裔 HIV 患者进行了这种变异的基因分型。对有明确血清转化日期的患者进行疾病进展分析，对有纵向病毒载量数据的患者进行病毒载量分析。我们进一步使用 HLA-C 特异性抗体检测了正常供体的 HLA-C 细胞表面表达。结果表明，-35C 等位基因是 HLA-C 细胞表面高表达的标志，与低 HLA-C 表达等位基因的个体相比，高表达 HLA-C 等位基因的个体进展为艾滋病的速度较慢，控制病毒载量的效果明显更好。这些数据强烈表明，HLA-C 表达水平较高可能通过更好地向细胞毒性 T 淋巴细胞呈递抗原，或通过自然杀伤细胞识别和杀伤感染细胞，从而更有效地控制 HIV-1。
