CD229 (Ly9) Lymphocyte Cell Surface Receptor Interacts Homophilically through Its N-Terminal Domain and Relocalizes to the Immunological Synapse 1

CD229 (Ly9) Lymphocyte Cell Surface Receptor Interacts Homophilically through Its N-Terminal Domain and Relocalizes to the Immunological Synapse 1
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CD229 (Ly9) 淋巴细胞表面受体通过其 N 端结构域发生同源相互作用并重新定位至免疫突触 1

DOI:
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发表时间:
2005
影响因子:
4.4
通讯作者:
P. Engel
P. Engel
中科院分区:
医学2区
文献类型:
--
作者:
X. Romero;N. Zapater;M. Calvo;S. Kalko;M. A. de la Fuente;V. Tovar;C. Ockeloen;P. Pizcueta;P. Engel

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CD229是免疫球蛋白超家族中CD150家族的成员,表达于T细胞和B细胞上。这个家族的受体调节细胞因子的产生和淋巴细胞和NK细胞的细胞毒作用。CD229的胞浆尾巴与SAP结合,SAP是一种在X连锁淋巴增殖性综合征中存在缺陷的蛋白质。为了确定CD229的配体,我们构建了含有人CD229的两个N端胞外区的可溶性Ig融合蛋白(CD229-Ig)。CD229-Ig与CD229转基因细胞结合,而与表达CD150家族其他受体的细胞无结合,表明CD229与CD229同源结合。人和小鼠的CD229都与自身相互作用。结构域缺失突变体表明,N-末端Ig-结构域介导了亲和性粘连。当预测的B-C环上的带电氨基酸E27和E29以及N-末端结构域F-G环上的R89突变为丙氨酸时,CD229-CD229的结合严重受损。相反,一个突变,R44A,增强了同性体的相互作用。共聚焦显微镜图像分析显示,在抗原依赖的免疫突触形成过程中,CD229重新定位到T和B细胞的接触区。因此,CD229是其自身的配体,并参与免疫突触。
CD229 is a member of the CD150 family of the Ig superfamily expressed on T and B cells. Receptors of this family regulate cytokine production and cytotoxicity of lymphocytes and NK cells. The cytoplasmic tail of CD229 binds to SAP, a protein that is defective in X-linked lymphoproliferative syndrome. To identify the CD229 ligand, we generated a soluble Ig fusion protein containing the two N-terminal extracellular domains of human CD229 (CD229-Ig). CD229-Ig bound to CD229-transfected cells, whereas no binding was detected on cells expressing other CD150 family receptors, showing that CD229 binds homophilically. Both human and mouse CD229 interacted with itself. Domain deletion mutants showed that the N-terminal Ig-domain mediates homophilic adhesion. CD229-CD229 binding was severely compromised when the charged amino acids E27 and E29 on the predicted B-C loop and R89 on the F-G loop of the N-terminal domain were mutated to alanine. In contrast, one mutation, R44A, enhanced the homophilic interaction. Confocal microscopy image analysis revealed relocalization of CD229 to the contact area of T and B cells during Ag-dependent immune synapse formation. Thus, CD229 is its own ligand and participates in the immunological synapse.
直接测量细胞表面蛋白 CD2 和 CD48 之间的异型粘附。
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