Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages.
Antigens in extracellular fluids can be processed and presented with major histocompatibility complex (MHC) class I molecules by a subset of antigen presenting cells (APCs). Chicken egg ovalbumin (Ova) linked to beads was presented with MHC class I molecules by these cells up to 10(4)-fold more efficiently than soluble Ova. This enhanced presentation was observed with covalently or noncovalently linked Ova and with beads of different compositions. A key parameter in the activity of these conjugates was the size of the beads. The APC that is responsible for this form of presentation is a macrophage. These cells internalize the antigen constructs through phagocytosis, since cytochalasin B inhibited presentation. Processing of the antigen and association with MHC class I molecules appears to occur intracellularly as presentation was observed under conditions where there was no detectable release of peptides into the extracellular fluids. When injected in vivo in C57BL/6 mice, Ova-beads, but not soluble Ova, primed CD4- CD8+ cytotoxic T lymphocytes (CTLs). Similar results were obtained in BALB/c mice immunized with beta-galactosidase-beads. The implications of these findings for development of nonliving vaccines that stimulate CTL immunity are discussed.
Division of Lymphocyte Biology, Dana-Farber Cancer Institute, Boston, MA 02115.
M
M
Kovacsovics-Bankowski
K
K
Clark
B
B
Benacerraf
K L
KL
Rock
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D001386:Azides / Q000494:pharmacology; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007700:Kinetics; D016399:Lymphoma, T-Cell / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D001386:Azides; D015395:Histocompatibility Antigens Class I; D003571:Cytochalasin B; D010047:Ovalbumin; D003847:Deoxyglucose