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主要组织相容性复合体II类α链和β链均参与CD4功能,这表明有序寡聚化在T细胞活化中起作用。

Involvement of both major histocompatibility complex class II alpha and beta chains in CD4 function indicates a role for ordered oligomerization in T cell activation.

作者信息

König R, Shen X, Germain R N

机构信息

Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1019, USA.

出版信息

J Exp Med. 1995 Sep 1;182(3):779-87. doi: 10.1084/jem.182.3.779.

Abstract

CD4 is a membrane glycoprotein on T lymphocytes that binds to the same peptide:major histocompatibility complex (MHC) class II molecule recognized by the antigen-specific receptor (TCR), thereby stabilizing interactions between the TCR and peptide;MHC class II complexes and promoting the localization of the src family tyrosine kinase p56lck into the receptor complex. Previous studies identified a solvent-exposed loop on the class II beta 2 domain necessary for binding to CD4 and for eliciting CD4 coreceptor activity. Here, we demonstrate that a second surface-exposed segment of class II is also critical for CD4 function. This site is in the alpha 2 domain, positioned in single class II heterodimers in such a way that it cannot simultaneously interact with the same CD4 molecule as the beta 2 site. The ability of mutations at either site to diminish CD4 function therefore indicates that specifically organized CD4 and/or MHC class II oligomers play a critical role in coreceptor-dependent T cell activation.

摘要

CD4是T淋巴细胞上的一种膜糖蛋白,它与抗原特异性受体(TCR)识别的相同肽:主要组织相容性复合体(MHC)II类分子结合,从而稳定TCR与肽;MHC II类复合物之间的相互作用,并促进src家族酪氨酸激酶p56lck定位到受体复合物中。先前的研究确定了II类β2结构域上一个暴露于溶剂中的环,它对于与CD4结合和引发CD4共受体活性是必需的。在这里,我们证明II类的第二个表面暴露片段对CD4功能也至关重要。该位点位于α2结构域中,在单个II类异二聚体中的定位方式使其不能与β2位点同时与同一个CD4分子相互作用。因此,任一位点的突变降低CD4功能的能力表明,特异性组织的CD4和/或MHC II类寡聚体在共受体依赖性T细胞活化中起关键作用。

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