Human immune response to cationized proteins. II. Characterization of interaction of cationized diphtheria toxoid with human mononuclear cells.
Cationized diphtheria toxoid (cDT) has previously been shown to be more effective than the native protein as an inducer of human antigen-specific T cell responses. In the present study, biotin-labeled antigen and flow cytometric analysis were used to examine the possibility that enhanced immunogenicity of cDT may be a consequence of preferential binding to antigen-presenting cells. Strong binding of cDT, relative to native antigen, was noted for both monocytes and B cells. Characteristics of binding were similar for both cell types, including rapid saturation, temperature independence, and inhibition by unlabeled cationized proteins. Although both B cells and monocytes bound cDT, only monocytes were effective in triggering T cell proliferation, possibly as a result of slow internalization of bound antigen by B cells. Definition of the target structures of cationized proteins may allow for the design of more efficient vaccines, which would be specifically targeted to antigen-presenting cells in vivo.
Farmer
J L
JL
Abbott Laboratories Diagnostics Division, New Markers R&D, Abbott Park, Illinois 60064.
Roberts
L A
LA
Rydzinski
M E
ME
Hilty
M D
MD
D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D002412:Cations; D004167:Diphtheria Toxin / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000737:chemistry
D002412:Cations; D004167:Diphtheria Toxin; D014612:Vaccines