Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Hum Immunol. 2014 Mar;75(3):234-8. doi: 10.1016/j.humimm.2013.12.007. Epub 2013 Dec 27.
Alternatively spliced isoforms of the major histocompatibility complex (MHC) class I genes have been reported in many different species and therefore alternative splicing has been observed to be an additional layer of diversity in the MHC class I region. Here we show the characterization of a HLA-A splice variant in the human peripheral blood mononuclear cells (named "HLA-AΔE3"). This transcript is characterized by the deletion of exon 3 that encodes the α2 domain of the full-length HLA-A protein. Cell surface biotinylation experiments indicated that HLA-AΔE3 is able to be transported to the cell surface, as a 34-KDa glycoprotein that is totally sensitive to endoglycosidase-H treatment. Under nonreducing conditions, HLA-AΔE3 can form disulfide-linked homodimers on the cell surface. Furthermore, co-immunoprecipitation studies revealed that HLA-AΔE3 could interact with full-length HLA-A, forming a heterodimeric complex. These findings suggest that the splice variants of HLA-A under steady-state conditions may have an important function in regulating immune homeostasis.
已经在许多不同物种中报道了主要组织相容性复合体（MHC）I 类基因的剪接异构体，因此，剪接被认为是 MHC I 区多样性的另一个层次。在这里，我们展示了人类外周血单核细胞中 HLA-A 剪接变体的特征（命名为“HLA-AΔE3”）。该转录本的特征是缺失编码全长 HLA-A 蛋白 α2 结构域的外显子 3。细胞表面生物素化实验表明，HLA-AΔE3 能够被运输到细胞表面，作为一种 34-KDa 的糖蛋白，完全对内切糖苷酶 H 处理敏感。在非还原条件下，HLA-AΔE3 可以在细胞表面形成二硫键连接的同源二聚体。此外，共同免疫沉淀研究表明，HLA-AΔE3 可以与全长 HLA-A 相互作用，形成异源二聚体复合物。这些发现表明，在稳态条件下 HLA-A 的剪接变体可能在调节免疫稳态方面具有重要功能。
