Characterization of Murine CD70, the Ligand of the TNF Receptor Family Member CD27

Human CD70 (CD27 ligand) is a type II transmembrane glycoprotein belonging to the TNF family. The protein is not expressed on resting lymphocytes, but is rapidly induced on these cells after cellular activation. Importantly, interaction of CD70 with its receptor CD27 gives a costimulatory signal for lymphocyte activation. Whereas CD27 has been molecularly characterized in the mouse, murine CD70 (mCD70) was undefined until now. Here, we describe the cDNA cloning and initial characterization of mCD70 and the determination of its gene structure. mCD70 is a polypeptide of 195 amino acids that has 62% homology with its human counterpart. In analogy to human CD70, mCD70 transcript levels are strongly but transiently up-regulated during lymphocyte activation, which is in line with a role for the CD27-CD70 receptor pair early in the immune response. In accordance with the comitogenic activity of mCD27-specific mAb, recombinant mCD70 potently costimulates T cell proliferation. Finally, the mCD70 gene consists of three exons spanning approximately 4 kb of DNA and is localized on chromosome 17.