Different Stabilities of the structurally related receptors for IgE and IgG on the cell surface are determined by length of the stalk region in their α-chains
Different Stabilities of the structurally related receptors for IgE and IgG on the cell surface are determined by length of the stalk region in their α-chains
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DOI：
10.4049/jimmunol.176.11.7008
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Karasuyama, Hajime
中科院分区：
文献类型：
--
作者：
Kubota, Toshiyuki;Mukai, Kaori;Karasuyama, Hajime
由α链和γ链组成而没有β链的高亲和力IgE受体Fc β RI的变体在人APC（如树突细胞）上表达，并且已经被认为促进通过IgE的Ag摄取，从而促进Ag呈递至T细胞。这些细胞上的Fc β RI水平与血清IgE浓度相关，表明IgE介导α γ 2型Fc β RI的上调。肥大细胞和嗜碱性粒细胞上IgE介导的Fc ε RI上调已显示增强这些细胞释放负责过敏性炎症反应的化学介质和细胞因子的能力。在此，为了阐明控制Fc γ RI表达的机制，我们比较了两种结构上相关的IG受体，人Fc γ RI和Fc γ RIIIA，它们携带不同的α链但相同的γ链。Fc γ RIIIA在细胞表面上的半衰期很短，除非其结合IgE，而Fc γ RIIIA在没有IgG结合的情况下稳定表达。Fc γ RHI α和Fc γ RHIII α链的非Ig结合部分的改组显示，茎区在决定其稳定性和配体诱导的上调差异方面至关重要。出乎意料的是，在茎区中添加或缺失氨基酸的分析强烈表明，茎区的长度而不是氨基酸序列在确定REM和Fc γ RIIIA在细胞表面上的不同稳定性方面具有主要重要性。这一发现提供了新的见解的机制调节表面Fc受体的表达。
A variant of the high affinity IgE receptor Fc epsilon RI, which is composed of alpha- and gamma-chains without the beta-chain, is expressed on human APC, such as dendritic cells, and has been suggested to facilitate Ag uptake through IgE and hence to facilitate Ag presentation to T cells. The level of Fc epsilon RI on these cells is correlated with the serum IgE concentration, suggesting IgE mediates the up-regulation of the alpha gamma 2-type Fc epsilon RI. The IgE-mediated Fc epsilon RI up-regulation on mast cells and basophils has been shown to enhance the ability of these cells to release chemical mediators and cytokines that are responsible for allergic inflammatory reactions. Here, to elucidate the mechanism controlling Fc epsilon RI expression, we compared two structurally related Ig receptors, human Fc epsilon RI and Fc gamma RIIIA, which carry different a-chains but the same gamma-chains. The half-life of Fc epsilon RI on the cell surface was short unless it bound IgE, whereas Fc gamma RIIIA was stably expressed without IgG binding. Shuffling of the non Ig-binding portions of the Fc epsilon RI alpha and Fc gamma RHIII alpha chains revealed that the stalk region was critical in determining the difference in their stability and ligand-induced up-regulation. Unexpectedly, analyses with added or deleted amino acids in the stalk region strongly suggested that the length rather than the amino acid sequence of the stalk region was of major importance in determining the different stabilities of REM and Fc gamma RIIIA on the cell surface. This finding provides new insights into the mechanism regulating surface Fc epsilon RI expression.