Relative expression levels of the HLA class-I proteins in normal and HIV-infected cells.
Relative expression levels of the HLA class-I proteins in normal and HIV-infected cells.
复制标题
DOI：
10.4049/jimmunol.1403234
复制
发表时间：
2015-04-15
期刊：
影响因子：
--
通讯作者：
Carrington M
中科院分区：
文献类型：
--
作者：
Apps R;Meng Z;Del Prete GQ;Lifson JD;Zhou M;Carrington M
已知人类白细胞抗原 (HLA) 的表达水平会影响病理结果：病原体下调 HLA 以逃避宿主免疫反应，宿主炎症反应上调 HLA，而人与人之间 HLA 稳态表达水平的差异与疾病易感性相关。然而，由于 HLA 具有巨大的多态性，因此很难精确定量各个 HLA 位点的相对表达水平。我们报告了特定单倍型 A*02:01、B*44:02、C*05:01 的 HLA-A、HLA-B、HLA-C 和 HLA-E 蛋白的相对表达水平，并使用基于流式细胞术和质谱法的两种独立方法进行了表征。正常供体的外周血淋巴细胞显示，HLA-A 和 HLA-B 蛋白的表达水平相似，通过流式细胞术检测为 HLA-C 的 13-18 倍，通过质谱检测为 HLA-C 的 4-5 倍，差异可能反映了检测到的蛋白质构象或位置的变化。通过质谱检测，HLA-E 的水平比 HLA-C 低 25 倍。由于 HIV 下调选择性 HLA 类型，因此还对体外感染 HIV 的原代 CD4+ T 细胞进行了研究。 HIV感染细胞上的HLA-A和-B减少的程度在受感染培养物中的细胞之间有所不同。通过流式细胞术对个体的所有感染细胞进行平均后发现，不同个体的 HLA-A 比 HLA-C 高 1-3 倍，HLA-B 比 HLA-C 高 2-5 倍。这些结果量化了来自不同 HLA 位点的蛋白质表达水平的显着差异，这对于未感染和 HIV 感染的细胞很可能具有生理意义。
The expression level of human leukocyte antigens (HLA) is known to influence pathological outcomes: pathogens downregulate HLA to evade host immune responses, host inflammatory reactions upregulate HLA, and differences between people in steady-state expression levels of HLA associate with disease susceptibility. Yet precise quantification of relative expression levels of the various HLA loci is difficult due to the tremendous polymorphism of HLA. We report relative expression levels of HLA-A, HLA-B, HLA-C and HLA-E proteins for the specific haplotype A*02:01, B*44:02, C*05:01, characterized using two independent methods based on flow cytometry and mass spectrometry. Peripheral blood lymphocytes from normal donors showed that HLA-A and HLA-B proteins are expressed at similar levels, which are 13-18 times higher than HLA-C by flow cytometry and 4-5 times higher than HLA-C by mass spectrometry, differences that may reflect variation in the conformation or location of proteins detected. HLA-E was detected at a level 25 times lower than that of HLA-C by mass spectrometry. Primary CD4+ T cells infected with HIV in vitro were also studied since HIV downregulates selective HLA types. HLA-A and -B were reduced on HIV-infected cells by a magnitude that varied between cells in an infected culture. Averaging all infected cells from an individual showed HLA-A to be 1-3 and HLA-B to be 2-5 times higher than HLA-C for different individuals by flow cytometry. These results quantify substantial differences in expression levels of the proteins from different HLA loci, which are very likely physiologically significant on both uninfected and HIV-infected cells.
登录
查看更多内容
影响因子：
2.6
作者：
Gough SC;Simmonds MJ
通讯作者：
Simmonds MJ
影响因子：
9.2
作者：
Braud, VM;Allan, DSJ;McMichael, AJ
通讯作者：
McMichael, AJ
影响因子：
5.4
作者：
BERETTA, A;GRASSI, F;SICCARDI, AG
通讯作者：
SICCARDI, AG
DOI：
10.4049/jimmunol.1400577
发表时间：
2014-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hiby SE;Apps R;Chazara O;Farrell LE;Magnus P;Trogstad L;Gjessing HK;Carrington M;Moffett A
通讯作者：
Moffett A
影响因子：
64.8
作者：
Kulkarni, Smita;Savan, Ram;Qi, Ying;Gao, Xiaojiang;Yuki, Yuko;Bass, Sara E.;Martin, Maureen P.;Hunt, Peter;Deeks, Steven G.;Telenti, Amalio;Pereyra, Florencia;Goldstein, David;Wolinsky, Steven;Walker, Bruce;Young, Howard A.;Carrington, Mary
通讯作者：
Carrington, Mary