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
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
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恒河猴 MHC I A 类及其正常剪接变体的β2-微球蛋白-游离异二聚化减少了 MHC I A 类的泛素依赖性降解
DOI：
10.4049/jimmunol.1100665
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发表时间：
2012-03
期刊：
影响因子：
--
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文献类型：
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MHC-I类(MHC-I)分子通过向CTL递呈抗原肽和调节NK细胞的杀伤活性，在免疫反应的调节中发挥关键作用。在这篇文章中，我们发现猕猴的MHC I A可以选择性地剪接，产生一种新的MHC I A亚型(称为“MHC I A-Sv1”)，不含α3结构域。尽管没有β-2微球蛋白(β-2M)，但MHC-A-SV1蛋白以糖苷酶H敏感糖蛋白的形式到达K562细胞表面，形成二硫键结合的同源二聚体。基于放线菌亚胺的蛋白追逐实验表明，在瞬时或稳定转染的细胞系中，MHC I A-SV1蛋白比全长MHC I A蛋白更稳定。特别值得注意的是，我们的研究表明，在哺乳动物细胞中，MHC IA-Sv1可以与其全长蛋白形成不含β2M的异源二聚体。异源二聚体的形成伴随着全长MHC I A泛素化的减少和随之而来的蛋白质的稳定。综上所述，这些结果表明，由于β2M的置换，MHC I A-Sv1和MHC I A可以形成一种新的异二聚体复合体，并阐明了在β2M自由异二聚化依赖的控制中调节MHC I A蛋白降解的相关性，这可能对MHC I A剪接变异体在经典MHC I A/TCR和MHC I A/杀伤细胞Ig样受体相互作用的微调中具有一定的意义。
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.
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DOI：
10.1084/jem.190.2.205
发表时间：
1999-07-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wang Z;Marincola FM;Rivoltini L;Parmiani G;Ferrone S
通讯作者：
Ferrone S
影响因子：
--
作者：
S. Kollnberger;P. Bowness
通讯作者：
S. Kollnberger;P. Bowness
影响因子：
4.4
作者：
G. G. Capps-G.;B. E. Robinson;K. Lewis;M. Zúñiga
通讯作者：
G. G. Capps-G.;B. E. Robinson;K. Lewis;M. Zúñiga
DOI：
10.1016/0167-5699(95)80127-8
发表时间：
1995-03
期刊：
Immunology today
影响因子：
--
作者：
F. Puppo;M. Scudeletti;F. Indiveri;S. Ferrone
通讯作者：
F. Puppo;M. Scudeletti;F. Indiveri;S. Ferrone
影响因子：
4.4
作者：
Lynch, Sarah;Santos, Susana G.;Powis, Simon J.
通讯作者：
Powis, Simon J.