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 recently been reported in the CD99-deficient lymphoblastoid B cell line displaying the characteristics of Hodgkin's and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surface is primarily due to a defect in the transport from the Golgi complex to the 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 assembly of MHC class I molecules and the transport from the endoplasmic reticulum 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 displayed the delayed transport of newly synthesized MHC class I molecules to the plasma membrane, thus causing accumulation of the molecules within the 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 post-Golgi trafficking machinery by regulating the transport to the plasma membrane rather than the endocytosis of surface MHC class I molecules, providing a novel mechanism of MHC class I down-regulation for immune escape.
Sohn
H W
HW
Department of. Pathology and Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Shin
Y K
YK
Lee
I S
IS
Bae
Y M
YM
Suh
Y H
YH
Kim
M K
MK
Kim
T J
TJ
Jung
K C
KC
Park
W S
WS
Park
C S
CS
Chung
D H
DH
Ahn
K
K
Kim
I S
IS
Ko
Y H
YH
Bang
Y J
YJ
Kim
C W
CW
Park
S H
SH
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001693:Biological Transport, Active / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004705:Endocytosis / Q000235:genetics / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger