Scholarlink

<p>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<sup>+</sup>CD56<sup>bright</sup> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HLA class I signal peptide variation predicts strength of NKG2A+ NK cell response to missing-self and risk of human disease

  • 期刊论文

  • 发表日期：

    2026年3月4日

查看全文
  • Zhansong Lin,
  • Arman A. Bashirova,
  • Cian Callahan,
  • George W. Nelson,
  • Emma Robinson,
  • Mathias Viard,
  • Minzhong Tang,
  • Allan Hildesheim,
  • Andre Franke,
  • John D. Rioux,
  • Wilfredo Garcia-Beltran,
  • Mary Carrington

摘要

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+CD56bright 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.