Ramsuran Veron, Naranbhai Vivek, Horowitz Amir, Qi Ying, Martin Maureen P, Yuki Yuko, Gao Xiaojiang, Walker-Sperling Victoria, Del Prete Gregory Q, Schneider Douglas K, Lifson Jeffrey D, Fellay Jacques, Deeks Steven G, Martin Jeffrey N, Goedert James J, Wolinsky Steven M, Michael Nelson L, Kirk Gregory D, Buchbinder Susan, Haas David, Ndung'u Thumbi, Goulder Philip, Parham Peter, Walker Bruce D, Carlson Jonathan M, Carrington Mary
Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Science. 2018 Jan 5;359(6371):86-90. doi: 10.1126/science.aam8825. Epub 2018 Jan 4.
The highly polymorphic human leukocyte antigen () locus encodes cell surface proteins that are critical for immunity. expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher levels confer poorer control of HIV. Elevated expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.
高度多态的人类白细胞抗原（）基因座编码对免疫至关重要的细胞表面蛋白。表达水平以等位基因依赖的方式变化，使等位基因特异性效应多样化，超出了肽结合偏好。对来自21个队列的9763名HIV感染者的分析表明，较高的水平会导致对HIV的控制较差。升高的表达提供了更高水平的一种源自HLA-A的信号肽，该信号肽特异性结合并决定抑制性NKG2A自然杀伤（NK）细胞受体的配体HLA-E的表达水平。有利于NKG2A介导的NK细胞许可（即教育）的单倍型会加剧高表达对HIV控制的有害影响，这与NKG2A介导的抑制损害NK细胞对HIV感染靶标的清除一致。对HLA-E:NKG2A相互作用的治疗性阻断可能会对HIV疾病有益。
