Nonionic triblock copolymers facilitate delivery of exogenous proteins into the MHC class I and class II processing pathways.
Nonionic triblock copolymers are relatively nontoxic adjuvants that induce high-titer, long-lasting antibody responses. We have previously shown that these adjuvants also induce cell-mediated immunity including lymphokine production by CD4(+) T cells and cytolytic responses by CD8(+) T cells. These copolymers are thought to modulate hydrophobic adhesive interactions between antigens (Ag) and lymphoid cells. We sought to test the hypothesis that copolymers facilitate uptake of exogenous Ag by antigen-presenting cells (APC) using an in vitro model system. Our data show that nonionic triblock copolymers enhanced presentation of soluble ovalbumin (OVA) to the major histocompatibility complex (MHC) class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells, respectively. Presentation of OVA via the class I pathway was enhanced by copolymers in both phagocytic and nonphagocytic APC. However, copolymers did not enhance binding of peptides to the MHC molecules on APC, presentation of endogenously synthesized Ag, or presentation of exogenous Ag delivered by electroporation. These results provide additional evidence that these nonionic triblock copolymers can serve as powerful adjuvants for augmenting both humoral and cell-mediated immunity to protein Ag.
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Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
McGraw
C L
CL
Hunter
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Kapp
J A
JA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology*; D011060:Poloxalene / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D013945:Thymoma; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011108:Polymers; D011060:Poloxalene; D010047:Ovalbumin