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Blood, 15 October 2001, Vol. 98, No. 8, pp. 2482-2488
IMMUNOBIOLOGY
HIV gp120 receptors on human dendritic cells
Stuart G. Turville,
Jim Arthos,
Kelli Mac
Donald,
Garry Lynch,
Hassan Naif,
Georgina Clark,
Derek Hart, and
Anthony L. Cunningham
From the Center For Virus Research, Westmead Millennium
Institute, Sydney, Australia; National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD; and
Mater Medical Research Institute, Brisbane, Australia.
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.

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