MHC class II expression in double mutant mice lacking invariant chain and DM functions.
MHC class II expression in double mutant mice lacking invariant chain and DM functions.
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DOI：
10.4049/jimmunol.160.2.606
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发表时间：
1998-01
影响因子：
4.4
通讯作者：
George Kenty;W. Martin;L. Van Kaer;E. Bikoff
中科院分区：
文献类型：
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作者：
George Kenty;W. Martin;L. Van Kaer;E. Bikoff
在II类成熟过程中的不同阶段需要不变（Ii）链和DM功能，以促进不同肽配体的占用。由缺乏Ii链或DM活性的突变小鼠品系表达的II类分子显示离散的结构和功能异常。本报告描述了Ii-DM-双缺陷小鼠的细胞和生化特征。至于Ii链突变体，它们的成熟Aalpha AbAbbeta二聚体在SDS-PAGE中类似地表现出降低的迁移率，并且在功能测定中，这些分子表现得好像是空的或被容易置换的肽占据。此外，本实验证明，松软的Aalphab Abetab二聚体的产生是TAP独立的。与Ii链突变体相比，Ii-DM-双缺陷细胞群体在T细胞刺激测定中表现出增加的肽结合活性和一贯更大的呈递能力。这些功能差异似乎反映了与其增加的B淋巴细胞代表性相关的较高的II类表面表达。我们还观察到缺乏Ii链或DM表达的小鼠中有缺陷的B细胞成熟，有趣的是，B细胞发育在Ii-DM-双突变体中表现出更严重的受损。这些突变小鼠缺乏Ii链和DM活动，应证明用于分析非常规的II类Ag介绍在正常生理条件下，在完整的动物。
Invariant (Ii) chain and DM functions are required at distinct stages during class II maturation to promote occupancy by diverse peptide ligands. The class II molecules expressed by mutant mouse strains lacking Ii chain or DM activities display discrete structural and functional abnormalities. The present report describes the cellular and biochemical characteristics of Ii-DM- doubly deficient mice. As for Ii chain mutants, their mature Aalphab Abetab dimers similarly exhibit reduced mobilities in SDS-PAGE, and in functional assays these molecules behave as if empty or occupied by an easily displaced peptide. Additionally, the present experiments demonstrate that the production of floppy Aalphab Abetab dimers is TAP independent. In comparison with Ii chain mutants, Ii-DM- doubly deficient cell populations exhibit increased peptide binding activities and consistently greater presentation abilities in T cell stimulation assays. These functional differences appear to reflect higher class II surface expression associated with their increased representation of B lymphocytes. We also observe defective B cell maturation in mice lacking Ii chain or DM expression, and interestingly, B cell development appears more severely compromised in Ii-DM- double mutants. These mutant mice lacking both Ii chain and DM activities should prove useful for analyzing nonconventional class II Ag presentation under normal physiological conditions in the intact animal.