Endogenously expressed HIV-1 nef down-regulates antigen-presenting molecules, not only class I MHC but also CD1a, in immature dendritic cells.
The effects of Nef molecules on immature dendritic cells (iDCs) were analyzed using recombinant human immunodeficiency virus type 1 (HIV-1) with intact nef gene, pseudotyped with vesicular stomatitis virus glycoprotein, HIV/VSV-G/+Nef. When iDCs were infected with HIV/VSV-G/+Nef, the surface expression of CD1a, a molecule for presenting glycolipid/lipid antigens, was selectively down-regulated among CD1 molecules (CD1a, -b, -c, and -d) as well as class I MHC. Moreover, the CD1a molecules were also down-modulated and co-localized with DsRed2-tagged-Nef in CD1a-transfected cells. Their co-localization was dependent upon CD1a cytoplasmic tail and the CD1a was redistributed from cell surface to LAMP-1+ late endosomal/lysosomal compartment. These findings reveal that the HIV-1-Nef interferes with the intracellular trafficking of CD1a, and suggest the involvement of CD1a-restricted immune effectors in the protective immunity against HIV-1 infection, which implicates the feasibility of virus-derived glycolipid/lipid antigens together with epitope peptides for the vaccine development.
Shinya
Eiji
E
Department of Microbiology and Immunology, Nippon Medical School, Bunkyo, Tokyo 113-8602, Japan.
Owaki
Atsuko
A
Shimizu
Masumi
M
Takeuchi
Junko
J
Kawashima
Tetsuo
T
Hidaka
Chizuno
C
Satomi
Misao
M
Watari
Eiji
E
Sugita
Masahiko
M
Takahashi
Hidemi
H
D015703:Antigens, CD / Q000276:immunology; D018949:Antigens, CD1 / Q000032:analysis*; D001692:Biological Transport; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015536:Down-Regulation; D011992:Endosomes / Q000276:immunology; D015693:Gene Products, nef / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006023:Glycoproteins; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D008164:Luminescent Proteins; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000276:immunology; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; D018949:Antigens, CD1; D015693:Gene Products, nef; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D008164:Luminescent Proteins; D051907:Lysosomal Membrane Proteins; C413663:fluorescent protein 583; D054311:nef Gene Products, Human Immunodeficiency Virus