Brossay Angélique, Hubé Florent, Moreau Thierry, Bardos Pierre, Watier Hervé
EA 3249 Cellules Hématopoïétiques, Hémostase et Greffe, Université François Rabelais, Tours, France.
Biochem Biophys Res Commun. 2003 Oct 3;309(4):992-8. doi: 10.1016/j.bbrc.2003.08.099.
The porcine ligands of human CD2 remain unknown in xenotransplantation despite being an important pathway of T cell costimulation. Of the two main candidates, i.e., CD48 and CD58, the cDNA of the most likely ligand poCD58 was cloned from CD48-negative endothelial cells costimulating human CD4(+) T cells through the CD2 pathway. The deduced protein sequence is 244 residues long and is 43% homologous to the human sequence. Based on similarity between porcine and human CD58 external V-set Ig-type domains, a structural model of poCD58-huCD2 interaction was built. Most of the charged residues located at the interface with huCD2 are highly conserved. Six putative hydrogen bonds between poCD58 and huCD2 were identified; five involve the same residues as in the syngeneic combination while the sixth is formed between an additional tyrosine in poCD58 and Arg48 in huCD2, increasing the complementarity between the two molecules. These structural data will help us to develop poCD58 blocking agents for xenotransplantation.
尽管人类CD2的猪源配体是T细胞共刺激的重要途径，但在异种移植中仍不清楚。在两个主要候选物，即CD48和CD58中，最可能的配体猪CD58的cDNA是从通过CD2途径共刺激人CD4(+) T细胞的CD48阴性内皮细胞中克隆出来的。推导的蛋白质序列长244个残基，与人类序列的同源性为43%。基于猪和人CD58外部V-set Ig型结构域之间的相似性，构建了猪CD58-人CD2相互作用的结构模型。位于与人类CD2界面处的大多数带电荷残基高度保守。鉴定出猪CD58与人CD2之间的六个推定氢键；其中五个涉及同基因组合中的相同残基，而第六个是由猪CD58中额外的酪氨酸与人类CD2中的Arg48之间形成的，增加了两个分子之间的互补性。这些结构数据将有助于我们开发用于异种移植的猪CD58阻断剂。
