Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor.
Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor.
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CTLA-4 受体存在与 B7 不同的额外配体的证据。
DOI：
10.1073/pnas.90.23.11182
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发表时间：
1993
影响因子：
11.1
通讯作者：
Reiser,H
中科院分区：
文献类型：
--
作者：
Razi-Wolf,Z;Galvin,F;Gray,G;Reiser,H
T淋巴细胞的激活需要识别肽-主要组织相容性复合体和抗原呈递细胞（APCs）提供的共刺激信号。迄今为止，表征最好的共刺激分子是B7抗原，它是免疫球蛋白家族的一员，可以结合表达在t细胞表面的两种受体CD28和CTLA-4。利用我们最近开发的抗小鼠B7 （mB7）单克隆抗体（mAb） 16-10A1，我们发现mB7确实是B淋巴细胞抗原特异性激活小鼠T细胞的重要共刺激配体。然而，有三条证据表明，至少存在一种额外的CTLA-4受体配体。首先，人CTLA-4和IgG1 Fc区的可溶性融合蛋白CTLA4Ig比抗mb7单抗更好地阻断未分离脾APCs对T细胞的异体刺激。其次，饱和量的抗mb7单抗不会显著阻断异硫氰酸荧光素偶联的CTLA4Ig与活化的脾apc的结合。此外，CTLA4Ig与M12和M12发生反应，而抗mb7单抗与M12不发生反应。C3细胞系。另外一种CTLA-4配体的鉴定可能应用于自身免疫性疾病和移植相关疾病的治疗。
Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complex complexes and costimulatory signals provided by antigen-presenting cells (APCs). The best-characterized costimulatory molecule to date is the B7 antigen, a member of the immunoglobulin family that binds two receptors, CD28 and CTLA-4, expressed on the T-cell surface. Using the anti-mouse B7 (mB7) monoclonal antibody (mAb) 16-10A1, which we recently developed, we found that mB7 is indeed an important costimulatory ligand for the antigen-specific activation of murine T cells by B lymphocytes. Three lines of evidence suggest, however, the existence of at least one additional ligand for the CTLA-4 receptor. First, a soluble fusion protein of human CTLA-4 and the IgG1 Fc region, termed CTLA4Ig, blocks better than the anti-mB7 mAb the allogeneic stimulation of T cells by unfractionated splenic APCs. Second, saturating amounts of anti-mB7 mAb do not significantly block binding of fluorescein isothiocyanate-conjugated CTLA4Ig to activated splenic APCs. Furthermore, CTLA4Ig but not the anti-mB7 mAb reacts with the M12 and M12.C3 cell lines. The identification of an additional ligand for CTLA-4 may have applications to the treatment of autoimmune disease and transplant-associated disorders.