Division of Gastroenterology, Department of Medicine, University of Alberta, 130 University Campus, Edmonton, Alberta, Canada.
Dev Comp Immunol. 2010 Jul;34(7):749-58. doi: 10.1016/j.dci.2010.02.004. Epub 2010 Feb 20.
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is an inhibitory T cell receptor predominately expressed on activated T cells. The duck CTLA-4 (DuCTLA-4) cDNA and a transcript lacking the predicted transmembrane encoding region (DuCTLA-4DeltaTM) were isolated from splenocytes using RT-PCR. The predicted DuCTLA-4 protein showed an identity of 92%, 49% and 47% with chicken, human and mouse homologues, respectively. Sequence comparison revealed conservation of residues implicated in the B7 ligand binding, disulfide linkages, glycosylation and intracellular signaling. DuCTLA-4 mRNA was predominately expressed in primary and secondary immune organs. DuCTLA-4 and DuCTLA-4DeltaTM transcripts were differentially regulated in PBMCs. Flow cytometric analysis showed constitutive expression of DuCTLA-4 protein on freshly isolated PBMCs and a modest increase upon mitogen stimulation. Our observations suggest that DuCTLA-4 and its isoform DuCTLA-4DeltaTM evolved before the divergence of birds and mammals. Both DuCTLA-4 isoforms have significant structural homology to mammalian CTLA-4 proteins but their individual roles in the regulation of duck immune responses remains to be elucidated.
细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4，CD152）是一种主要表达于激活 T 细胞上的抑制性 T 细胞受体。鸭 CTLA-4（DuCTLA-4）cDNA 和一个缺少预测跨膜编码区的转录本（DuCTLA-4DeltaTM）是通过 RT-PCR 从脾细胞中分离出来的。预测的 DuCTLA-4 蛋白与鸡、人、鼠同源物的同源性分别为 92%、49%和 47%。序列比较显示，与 B7 配体结合、二硫键、糖基化和细胞内信号转导有关的残基保守。DuCTLA-4 mRNA 主要在初级和次级免疫器官中表达。DuCTLA-4 和 DuCTLA-4DeltaTM 转录本在 PBMCs 中的表达存在差异调节。流式细胞术分析显示，新鲜分离的 PBMCs 上持续表达 DuCTLA-4 蛋白，而在有丝分裂原刺激下略有增加。我们的观察结果表明，DuCTLA-4 和它的同工型 DuCTLA-4DeltaTM 在鸟类和哺乳动物分化之前就已经进化了。两种 DuCTLA-4 同工型与哺乳动物 CTLA-4 蛋白具有显著的结构同源性，但它们在调节鸭免疫反应中的各自作用仍有待阐明。
