The luminal part of the murine cytomegalovirus glycoprotein gp40 catalyzesthe retention of MHC class I molecules

Murine cytomegalovirus (MCMV) interferes with the MHC class I pathway of an tigen presentation. The type I transmembrane glycoprotein gp40, encoded by the gene m152, retains major histocompatibility complex (MHC) class I compl exes in the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGI C)/cis-Golgi. These MHC class I complexes are stable, show an extended half -life and do not exchange Pz-microglobulin, whereas gp40 reaches an endosom al/ lysosomal compartment where it subsequently is degraded. The analysis o f regions within the viral protein that are essential for MHC class I reten tion revealed that a secreted form of gp40, lacking the cytoplasmic tail an d the transmembrane region, still has the capacity to retain MHC class I co mplexes, Continuous expression of gp40 is not required for MHC class I rete ntion, Our data indicate that the retention of MHC class I complexes in the ERGIC/ cis-Golgi is triggered by gp40 and does not require the further pre sence of the viral protein.