Dendritic cells (DCs) are important targets for human immunodeficiency viru
s (HIV) because of their roles during transmission and also maintenance of
immune competence. Furthermore, DCs are a key cell in the development of HI
V vaccines. In both these settings the mechanism of binding of the HIV enve
lope 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 (MD-DCs) rather than CD4. In this study a novel bio
tinylated gp120 assay was used to determine whether CLR or CD4 were predomi
nant receptors on MDDCs and ex vivo blood DCs. CLR bound more than 80% of g
p120 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, man
nose receptor, and unidentified trypsin resistant CLR(s). In marked contras
t, freshly isolated and cultured CD11c(+ve) and CD11c(-ve) blood DCs only b
ound gp120 via CD4. In view of these marked differences between MDDCs and b
lood 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. (Blood. 2001;98:2482-2488) (C) 2001 by The American Society
of Hematology.