HIV gp120 receptors on human dendritic cells.
Dendritic cells (DCs) are important targets for human immunodeficiency virus (HIV) because of their roles during transmission and also maintenance of immune competence. Furthermore, DCs are a key cell in the development of HIV vaccines. In both these settings the mechanism of binding of the HIV envelope protein gp120 to DCs is of importance. Recently a single C-type lectin receptor (CLR), DC-SIGN, has been reported to be the predominant receptor on monocyte-derived DCs (MDDCs) rather than CD4. In this study a novel biotinylated gp120 assay was used to determine whether CLR or CD4 were predominant receptors on MDDCs and ex vivo blood DCs. CLR bound more than 80% of gp120 on MDDCs, with residual binding attributable to CD4, reconfirming that CLRs were the major receptors for gp120 on MDDCs. However, in contrast to recent reports, gp120 binding to at least 3 CLRs was observed: DC-SIGN, mannose receptor, and unidentified trypsin resistant CLR(s). In marked contrast, freshly isolated and cultured CD11c(+ve) and CD11c(-ve) blood DCs only bound gp120 via CD4. In view of these marked differences between MDDCs and blood DCs, HIV capture by DCs and transfer mechanisms to T cells as well as potential antigenic processing pathways will need to be determined for each DC phenotype.
Turville
S G
SG
Center for Virus Research, Westmead Millennium Institute, Sydney, Australia.
Arthos
J
J
Donald
K M
KM
Lynch
G
G
Naif
H
H
Clark
G
G
Hart
D
D
Cunningham
A L
AL
D016915:AIDS Vaccines; D001665:Binding Sites; D001692:Biological Transport; D015704:CD4 Antigens / Q000502:physiology; D037222:Collectins; D003713:Dendritic Cells / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000502:physiology / Q000821:virology; D015728:Receptors, HIV / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014357:Trypsin / Q000378:metabolism; D014614:Vaccines, Synthetic
D016915:AIDS Vaccines; D015704:CD4 Antigens; C422442:COLEC12 protein, human; D037222:Collectins; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014357:Trypsin