Influence of HLA-C Expression Level on HIV Control
Influence of HLA-C Expression Level on HIV Control
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DOI：
10.1126/science.1232685
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发表时间：
2013-04-05
期刊：
影响因子：
56.9
通讯作者：
Carrington, Mary
中科院分区：
文献类型：
--
作者：
Apps, Richard;Qi, Ying;Carrington, Mary
人类白细胞抗原C(人类白细胞抗原C)上游的一个变异体在全基因组范围内对欧洲裔美国人的HIV控制产生了最显著的影响，也与人类白细胞抗原C的表达水平有关。我们对所有常见的人类白细胞抗原-C同种异型的细胞表面表达水平进行了表征，并在5243名个体中直接测试了人类白细胞抗原-C的表达对HIV感染结局的影响。在非洲和欧洲裔美国人中，无论其不同的HLA-C频率以及与HLA-B和HLA-A的连锁关系如何，在非洲和欧洲美国人中，增加的HLA-C表达与对多种结果的保护无关，独立于个体的HL A等位基因影响。人类白细胞抗原-C的高表达与细胞毒性T淋巴细胞反应的可能性和病毒逃逸突变的频率增加相关。相反，人类白细胞抗原-C的高表达在克罗恩病中有有害的影响，表明人类疾病中人类白细胞抗原的表达水平有更广泛的影响。
A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.