Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand; The Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
The Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; Department of Clinical Immunology and Transfusion Sciences, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Hum Immunol. 2024 Sep;85(5):111085. doi: 10.1016/j.humimm.2024.111085. Epub 2024 Aug 7.
The major histocompatibility complex (MHC) class I chain-related A (MICA) plays an important role in stress cell recognition. High polymorphisms of MICA are relevant to NKG2D binding capacity, responses of NK cells and tumor progression. In this study, MICA genotyping of 97 cholangiocarcinoma patients was performed using PCR-SSP. MICA010 was positively associated with a corrected p-value of < 0.001 (RR=2.16 (95 % CI, 1.48-3.14)). MICA010 was previously reported as a non-expressed allele. Thus, the expression of MICA010 on the cell surface was studied on both MICA010 transfected cells (HEK 293 T and L929 cells) and stimulated primary monocytes obtained from homozygous MICA010 individuals using different clones of antibodies (1H10, 1D10, 1C3.1, 1C3.2, 6D4 and 3H5) for detection. Surprisingly, the expression of MICA010 could be observed on both transfected cells and stimulated monocytes and effectively bound to the NKG2D-Fc fusion protein. The functional study of various MICA alleles revealed the high relative killing activity of NK cells induced by the MICA010 transfected C1R cells, not following the previously reported rule of the M129V substitution. The structural analysis highlighted the amino acid at position 36 as another important amino acid relevant to preserving the structural integrity of the MICA protein and NKG2D binding. Our data propose a new aspect of functional MICA contributing motifs and that MICA010 has a potential effect on NK cell functions and might be applicable to other fields of immune responses.
主要组织相容性复合体 I 类链相关 A（MICA）在应激细胞识别中发挥重要作用。MICA 的高度多态性与 NKG2D 结合能力、NK 细胞反应和肿瘤进展有关。在这项研究中，使用 PCR-SSP 对 97 例胆管癌患者的 MICA 基因分型进行了分析。MICA010 与校正后的 P 值<0.001（RR=2.16（95%CI，1.48-3.14））呈正相关。MICA010 之前被报道为一种非表达等位基因。因此，在 MICA010 转染细胞（HEK 293T 和 L929 细胞）和从纯合 MICA010 个体中获得的刺激原代单核细胞上研究了 MICA010 表面的表达，使用不同克隆的抗体（1H10、1D10、1C3.1、1C3.2、6D4 和 3H5）进行检测。令人惊讶的是，在转染细胞和刺激的单核细胞上都可以观察到 MICA010 的表达，并能有效地与 NKG2D-Fc 融合蛋白结合。对各种 MICA 等位基因的功能研究表明，MICA010 转染的 C1R 细胞诱导的 NK 细胞相对杀伤活性较高，不符合之前报道的 M129V 取代规则。结构分析突出了位置 36 的氨基酸是另一个与 MICA 蛋白和 NKG2D 结合的结构完整性相关的重要氨基酸。我们的数据提出了一个新的功能 MICA 贡献基序方面，并且 MICA010 对 NK 细胞功能有潜在影响，并且可能适用于其他免疫反应领域。
