目前普遍認為基因的選擇性剪接即基因選擇不同的剪接位點組合，是機體增加蛋白多樣性的一種有效方式，也是機體調控蛋白表達的一種重要機制。在人類和靈長類動物中，保守估計約有75%的基因發生選擇性剪接，尤其多發生在免疫系統。一個的免疫系統必須適時、適當地對病原微生物做出免疫應答。而免疫應答是機體免疫系統對抗原刺激所產生的以清除病源微生物為目的的生理過程。

“主要組織相容性復合物（MHC）是廣泛存在于脊椎動物體內與免疫功能密切相關的一組基因群，其基因產物不僅參與移植排斥和T淋巴細胞的分化發育，在機體免疫應答的啟動和免疫調節中也發揮重要作用。”戴正喜說，“許多研究表明，主要組織相容性復合物I類基因，在不同物種中均會發生不同程度的選擇性剪接，產生新的剪接異構體。但幾乎不清楚它怎樣精細調控免疫系統。”

為探討剪接異構體對全長型的MHCIA分子的影響及其在免疫調控中的作用，戴正喜等以人類近親獼猴為模型動物，在獼猴外周血中具有單個核的細胞中發現和鑒定了一種新的剪接異構體。通過生物化學和分子生物學實驗研究發現：這種新的剪接異構體可以表達于細胞膜表面，并且它的糖基化模式和蛋白降解速度與全長型的MHCIA分子明顯不同。

更有趣的是，它們倆能在細胞內形成一種全新的異源二聚體結構。進一步研究還發現，此異源復合體能促進MHCIA蛋白的穩定性。這種新的順式調控模式，為理解其對免疫應答的影響提供了一種全新視角。

該項研究獲得專家高度認可，他們一致認為是主要組織相容性復合物剪接領域的一項重要進展。

原文摘要：

The β2-Microglobulin–Free Heterodimerization of Rhesus Monkey MHC Class I A with Its Normally Spliced Variant Reduces the Ubiquitin-Dependent Degradation of MHC Class I A

Zheng-Xi Dai,Gao-Hong Zhang, Xi-He Zhang, Hou-Jun Xia, Shao-You Li and Yong-Tang Zheng

The MHC class I （MHC I） molecules play a pivotal role in the regulation of immune responses by presenting antigenic peptides to CTLs and by regulating cytolytic activities of NK cells. In this article, we show that MHC I A in rhesus macaques can be alternatively spliced, generating a novel MHC I A isoform （termed “MHC I A-sv1”） devoid of α3 domain. Despite the absence of β2-microglobulin （β2m）, the MHC I A-sv1 proteins reached the cell surface of K562-transfected cells as endoglycosidase H-sensitive glycoproteins that could form disulfide-bonded homodimers. Cycloheximide-based protein chase experiments showed that the MHC I A-sv1 proteins were more stable than the full-length MHC I A in transiently or stably transfected cell lines. Of particular interest, our studies demonstrated that MHC I A-sv1 could form β2m-free heterodimers with its full-length protein in mammalian cells. The formation of heterodimers was accompanied by a reduction in full-length MHC I A ubiquitination and consequent stabilization of the protein. Taken together, these results demonstrated that MHC I A-sv1 and MHC I A can form a novel heterodimeric complex as a result of the displacement of β2m and illustrated the relevance of regulated MHC I A protein degradation in the β2m-free heterodimerization-dependent control, which may have some implications for the MHC I A splice variant in the fine tuning of classical MHC I A/TCR and MHC I A/killer cell Ig-like receptor interactions.