HLA-B等位基因与不同病理学结果相关，包括自身免疫性疾病和恶性肿瘤。编码的HLA-B蛋白在抗原呈递给细胞毒性T细胞方面起着关键作用，一些包含Bw4模式的变异体也是杀伤性免疫球蛋白样受体（KIR）3DL1/S1的NK细胞配体。我们对急性髓系白血病（AML）复发预防免疫治疗中HLA-B基因型对疗效的潜在影响进行了研究。对78名非移植的AML患者在巩固阶段接受HDC/IL-2治疗进行了HLA-B和KIR基因的基因型分析。HLA-B*44与LFS（白血病无瘤生存）和总体生存（OS）降低相关，但这种与结果的负相关性在HLA-B44超型等位基因中并不共享。值得注意的是，HLA-B*44是少数带有Bw4模式并且在位置80处具有苏氨酸的HLA-B44超型等位基因之一，这通常导致与抑制性NK受体KIR3DL1的结合较弱。因此，KIR3DL1与Bw4之间的强相互作用与较好的LFS和OS相关（p = 0.014和p = 0.027）。来自80T-Bw4供体的KIR3DL1+ NK细胞显示出较低的脱颗粒反应和细胞因子反应，这表明80T-Bw4受试者中KIR3DL1介导的教育受损。我们提出，强的KIR3DL1+-Bw4相互作用的存在改善了NK细胞的教育，在接受HDC/IL-2免疫治疗预防复发的AML患者中具有优势。© 2023. The Author(s).

HLA-B alleles are associated with outcomes in various pathologies, including autoimmune diseases and malignancies. The encoded HLA-B proteins are pivotal in antigen presentation to cytotoxic T cells, and some variants containing a Bw4 motif also serve as ligands to the killer immunoglobulin-like receptors (KIR) 3DL1/S1 of NK cells. We investigated the potential impact of HLA-B genotypes on the efficacy of immunotherapy for relapse prevention in acute myeloid leukemia (AML). Seventy-eight non-transplanted AML patients receiving HDC/IL-2 in the post-consolidation phase were genotyped for HLA-B and KIR genes. HLA-B*44 heralded impaired LFS (leukemia-free survival) and overall survival (OS), but the negative association with outcome was not shared across alleles of the HLA-B44 supertype. Notably, HLA-B*44 is one of few HLA-B44 supertype alleles containing a Bw4 motif with a threonine at position 80, which typically results in weak binding to the inhibitory NK receptor, KIR3DL1. Accordingly, a strong interaction between KIR3DL1 and Bw4 was associated with superior LFS and OS (p = 0.014 and p = 0.027, respectively). KIR3DL1+ NK cells from 80 T-Bw4 donors showed significantly lower degranulation responses and cytokine responses than NK cells from 80I-Bw4 donors, suggesting impaired KIR3DL1-mediated education in 80 T-Bw4 subjects. We propose that presence of a strong KIR3DL1+-Bw4 interaction improves NK cell education and thus is advantageous in AML patients receiving HDC/IL-2 immunotherapy for relapse prevention.© 2023. The Author(s).