肿瘤细胞治疗研究
英文原题：HLA class I signal peptide variation predicts strength of NKG2A(+) NK cell response to missing-self and risk of human disease.
表达识别自身人类白细胞抗原（HLA）I类分子的抑制性受体的自然杀伤（NK）细胞获得增强的功能——这一过程受遗传多态性影响，该多态性决定了抑制性受体与其HLA配体之间相互作用的强度。
表达抑制性受体的自然杀伤（NK）细胞识别自身人类白细胞抗原（HLA）I类分子后获得增强的功能——这一过程受遗传多态性影响，该多态性决定了抑制性受体与其HLA配体之间相互作用的强度。抑制性CD94/NKG2A结合负载有来源于多态性HLA I类信号肽（SP）表位的HLA-E。我们构建了一个称为SP评分的指标，基于个体的SP基因型量化CD94/NKG2A-HLA-E相互作用的总体强度。SP评分与NKG2A+CD56bright NK细胞对HLA I类阴性细胞的反应呈正相关，表明CD94/NKG2A-HLA-E相互作用强度促进NK细胞教育。与此一致，较高的SP评分与较低的鼻咽癌和溃疡性结肠炎风险相关。因此，SP评分可作为指导临床NK细胞干预策略（包括治疗性NKG2A阻断）的遗传学工具。
Natural killer (NK) cells expressing inhibitory receptors that recognize self human leukocyte antigen (HLA) class I molecules gain enhanced functionality-a process influenced by genetic polymorphism that dictates the strength of interactions between inhibitory receptors and their HLA ligands. Inhibitory CD94/NKG2A binds HLA-E loaded with epitopes derived from polymorphic HLA class I signal peptides (SPs). We generated a metric, called SP score, that quantifies the overall strength of CD94/NKG2A-HLA-E interactions based on a person's SP genotype. SP scores correlated positively with NKG2A + CD56 bright NK cell response to HLA class I-negative cells, indicating that CD94/NKG2A-HLA-E interaction strength promotes NK cell education. Concordantly, higher SP scores associated with lower risk of nasopharyngeal carcinoma and ulcerative colitis. Thus, the SP score may serve as a genetic tool to guide clinical NK cell intervention strategies, including therapeutic NKG2A blockade.
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