Stalk region of beta-chain enhances the coreceptor function of CD8.
Stalk region of beta-chain enhances the coreceptor function of CD8.
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发表时间：
2003
影响因子：
4.4
通讯作者：
Jenny S. Wong;Xiaosong Wang;T. Witte;L. Nie;Nicolas Carvou;P. Kern;Hsiu-Ching Chang
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文献类型：
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作者：
Jenny S. Wong;Xiaosong Wang;T. Witte;L. Nie;Nicolas Carvou;P. Kern;Hsiu-Ching Chang
CD 8糖蛋白在T细胞表面表达为α α同二聚体或α β异二聚体。对于TCR识别肽Ag，CD 8 α是比CD 8 α α更有效的辅助受体。每个CD 8亚基由四个结构域组成，即Ig样结构域、茎区、跨膜区和胞质结构域。为了理解为什么CD 8 α是一种比CD 8 α α更好的辅助受体，我们设计、表达并功能性测试了一种嵌合的CD 8 α蛋白，其茎区被CD 8 β取代。我们发现，β柄区增强嵌合CD 8 α α的辅助受体功能的水平类似于CD 8 α。令人惊讶的是，β茎区也恢复了失活的CD 8 α变体的功能活性，该变体在Arg（8）（R8 A）处携带Ala突变，达到与野生型CD 8 α相似的水平。使用CD 8 α的R8 A变体、一组抗CD 8 α Ab和三种MHC I类（MHCI）变体，所述变体在已知参与CD 8 α相互作用的关键残基上不同，我们表明，CD 8 β茎的引入导致CD 8 α-MHCI复合物的不同拓扑结构，而不改变IG的整体结构。类似于CD 8 α的结构域或导致MHCI使用不同的残基与CD 8 α IG结构域相互作用。我们的研究结果表明，CD 8 β的茎区是能够微调作为辅助受体的CD 8蛋白的辅助受体功能，可能是由于其独特的蛋白质结构，较小的物理尺寸和独特的聚糖加合物与该地区。
CD8 glycoproteins are expressed as either alphaalpha homodimers or alphabeta heterodimers on the surface of T cells. CD8alphabeta is a more efficient coreceptor than the CD8alphaalpha for peptide Ag recognition by TCR. Each CD8 subunit is composed of four structural domains, namely, Ig-like domain, stalk region, transmembrane region, and cytoplasmic domain. In an attempt to understand why CD8alphabeta is a better coreceptor than CD8alphaalpha, we engineered, expressed, and functionally tested a chimeric CD8alpha protein whose stalk region is replaced with that of CD8beta. We found that the beta stalk region enhances the coreceptor function of chimeric CD8alphaalpha to a level similar to that of CD8alphabeta. Surprisingly, the beta stalk region also restored functional activity to an inactive CD8alpha variant, carrying an Ala mutation at Arg(8) (R8A), to a level similar to that of wild-type CD8alphabeta. Using the R8A variant of CD8alpha, a panel of anti-CD8alpha Abs, and three MHC class I (MHCI) variants differing in key residues known to be involved in CD8alpha interaction, we show that the introduction of the CD8beta stalk leads to a different topology of the CD8alpha-MHCI complex without altering the overall structure of the Ig-like domain of CD8alpha or causing the MHCI to employ different residues to interact with the CD8alpha Ig domain. Our results show that the stalk region of CD8beta is capable of fine-tuning the coreceptor function of CD8 proteins as a coreceptor, possibly due to its distinct protein structure, smaller physical size and the unique glycan adducts associated with this region.