The immunoglobulin superantigen-binding site of HIV-1 gp120 activates human basophils.
OBJECTIVE
To investigate the mechanism whereby HIV-1 envelope glycoprotein gp120 from four different isolates obtained in three different countries induces proinflammatory mediator release from normal human basophils.


METHODS
Histamine, cysteinyl leukotriene C4 (LTC4) and interleukin 4 (IL-4) release into the supernatant was measured in gp120-stimulated peripheral blood basophils from HIV-1 and HIV-2 negative subjects.


RESULTS
The HIV glycoprotein was a potent stimulus for release of these mediators in basophils purified from donors negative for HIV-1 and HIV-2. There was also a correlation (r = 0.58; P < 0.01) between the maximum IL-4 release from basophils induced by gp120 and by anti-IgE. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to gp120 and anti-IgE. Anti-IgE specifically desensitized basophils to a subsequent challenge with anti-IgE and gp120. Human monoclonal IgM carrying the VH3 domain, but not that carrying the VH6 domain, inhibited gp120-induced secretion of histamine from basophils in a concentration-dependent manner. Synthetic peptides identical to regions distant from the N- and C-termini of gp120MN inhibited its activating capacity.


CONCLUSIONS
gp120 acts as a viral superantigen interacting with the VH3 domain of IgE to induce the release of preformed and de novo synthesized mediators from human cells carrying the Fc fragment Fc epsilonRI receptor.
Florio
G
G
Division of Clinical Immunology and Allergy, University of Naples Federico II, Italy.
Petraroli
A
A
Patella
V
V
Triggiani
M
M
Marone
G
G
D000328:Adult; D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D015498:HIV-2 / Q000276:immunology; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D007700:Kinetics; D017997:Leukotriene C4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D015699:HIV Envelope Protein gp120; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D015289:Leukotrienes; D010455:Peptides; D017455:Receptors, IgE; D018089:Superantigens; C112381:cysteinyl-leukotriene; D015847:Interleukin-4; D017997:Leukotriene C4; D007073:Immunoglobulin E; D016572:Cyclosporine; D003545:Cysteine; D016559:Tacrolimus