Interaction of human epidermal Langerhans cells with HIV-1 viral envelope proteins (gp 120 and gp 160s) involves a receptor-mediated endocytosis independent of the CD4 T4A epitope.
The CD4 molecule is known to be the preferential receptor for the HIV-1 envelope glycoprotein. Epidermal Langerhans cells are dendritic cells which express several surface antigens, among them CD4 antigens. To clarify the exact role of CD4 molecules in Langerhans cell infection induced by HIV-1, we investigated the possible involvement of the interactions between HIV-1 gp 120 or HIV-1 gp 160s (soluble gp 160) and Langerhans cell surface. We also assessed the expression of CD4 molecules on Langerhans cell membranes dissociated by means of trypsin from their neighbouring keratinocytes. The cellular phenotype was monitored using flow cytometry and quantitative immunoelectron microscopy. We reported that human Langerhans cells can bind the viral envelope proteins (gp 120 or gp 160s), and that this binding does not depend on CD4 protein expression. This binding is not blocked by anti-CD4 monoclonal antibodies. We show that a proportion of gp 120/gp 160s-receptor complexes enters Langerhans cells by a process identified as a receptor-mediated endocytosis. The amount of surface bound gp 120/gp 160s is not consistent with the amount of CD4 antigens present on Langerhans cell membranes. Gp 120/gp 160s binding sites on Langerhans cell suspensions appeared to be trypsin resistant, while CD4 antigens (at least the epitopes known to bind the HIV-1) are trypsin sensitive. A burst of gp 120 receptor expression was detected on 1-day cultured Langerhans cells while CD4 antigens disappeared. These findings lead to the most logical conclusion that binding of gp 120/gp 160s is due to the presence of a Langerhans cell surface molecule different from CD4 antigens.
Dezutter-Dambuyant
C
C
INSERM U209, Laboratoire de Recherche Dermatologique et Immunologie, Hôpital Edouard Herriot, Lyon, France.
Schmitt
D A
DA
Dusserre
N
N
Hanau
D
D
Kolbe
H V
HV
Kieny
M P
MP
Cazenave
J P
JP
Schmitt
D
D
Pasquali
J L
JL
Olivier
R
R
D000954:Antigens, Surface / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D015704:CD4 Antigens / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000648:ultrastructure; D004705:Endocytosis / Q000276:immunology; D000078404:Epidermal Cells; D000939:Epitopes; D015686:Gene Products, env / Q000276:immunology* / Q000648:ultrastructure; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000648:ultrastructure; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D011498:Protein Precursors / Q000276:immunology* / Q000648:ultrastructure; D015728:Receptors, HIV / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D014357:Trypsin / Q000494:pharmacology
D000954:Antigens, Surface; D015704:CD4 Antigens; D000939:Epitopes; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D015728:Receptors, HIV; D014357:Trypsin