CD99 regulates the transport of MHC class I molecules from the Golgi complex to the cell surface

The down-regulation of surface expression of MHC class I molecules has rece ntly been reported in the CD99-deficient lymphoblastoid B cell line display ing the characteristics of Hodgkin's and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surfac e is primarily due to a defect in the transport from the Golgi complex to t he plasma membrane. Loss of CD99 did not affect the steady-state expression levels of mRNA and protein of MHC class I molecules. In addition, the asse mbly of MHC class I molecules and the transport from the endoplasmic reticu lum to the cis-Golgi occurred normally in the CD99-deficient cells, and no difference was detected between the CD99-deficient and the control cells in the pattern and degree of endocytosis. Instead, the CD99-deficient cells d isplayed the delayed transport of newly synthesized MHC class I molecules t o the plasma membrane, thus causing accumulation of the molecules within th e cells. The accumulated MHC class I molecules in the CD99-deficient cells were colocalized with alpha -mannosidase II and gamma -adaptin in the Golgi compartment, These results suggest that CD99 may be associated with the po st-Golgi trafficking machinery by regulating the transport to the plasma me mbrane rather than the endocytosis of surface MHC class I molecules, provid ing a novel mechanism of MHC class I downregulation for immune escape.