Huard B, Prigent P, Tournier M, Bruniquel D, Triebel F
Laboratoire d'Immunologie Cellulaire, INSERM U333, Institut Gustave-Roussy, Villejuif, France.
Eur J Immunol. 1995 Sep;25(9):2718-21. doi: 10.1002/eji.1830250949.
We analyzed CD4 major histocompatibility complex (MHC) class II interactions with CD4 and lymphocyte activation gene (LAG)-3 recombinant fusion proteins termed CD4Ig and LAG-3Ig. CD4Ig bound MHC class II molecules expressed on the cell surface only when used in the micromolar range. This weak CD4Ig binding was specific, since it was inhibited by anti-CD4 and anti-MHC class II mAb. LAG-3Ig bound MHC class II molecules with intermediate avidity (Kd = 60 nM at 37 degrees C). Using LAG-3Ig as a competitor in a CD4/MHC class II-dependent cellular adhesion assay, we showed that this recombinant molecule was able to block CD4/MHC class II interaction. In contrast, no inhibition was observed in a CD4/MHC class II-dependent T cell cytotoxicity assay. Together, these results suggest that co-engagement of the TcR with CD4 alters the CD4/MHC class II molecular interaction to become insensitive to LAG-3Ig competition.
我们分析了CD4主要组织相容性复合体（MHC）II类分子与称为CD4Ig和LAG-3Ig的CD4及淋巴细胞激活基因（LAG）-3重组融合蛋白的相互作用。只有在微摩尔范围内使用时，CD4Ig才会与细胞表面表达的MHC II类分子结合。这种较弱的CD4Ig结合具有特异性，因为它可被抗CD4和抗MHC II类单克隆抗体抑制。LAG-3Ig以中等亲和力结合MHC II类分子（37℃时Kd = 60 nM）。在依赖CD4/MHC II类分子的细胞黏附试验中，使用LAG-3Ig作为竞争者，我们发现这种重组分子能够阻断CD4/MHC II类分子的相互作用。相反，在依赖CD4/MHC II类分子的T细胞细胞毒性试验中未观察到抑制作用。总之，这些结果表明，T细胞受体与CD4的共同结合改变了CD4/MHC II类分子的相互作用，使其对LAG-3Ig竞争不敏感。
