Immune complex-mediated antigen presentation induces tumor immunity.
Antigen uptake receptors on dendritic cells (DCs) provide efficient entry for the initiation of antigen-specific adaptive immunity. Here we show that targeting of antigen to Fc receptors on DCs accomplishes combined activation of Th1 CD4 and CD8 effector responses in vivo, namely delayed-type hypersensitivity and tumor immunity. Tumor immunity specific for ovalbumin-expressing tumors was provided by immunization with wild-type but not FcgammaRgamma(-/-) DCs loaded with ovalbumin-containing immune complexes. Tumor protection was eliminated when immune complex-loaded DCs lacked beta(2) microglobulin, TAP, or MHC class II, demonstrating that Fc receptor-targeted antigenic uptake led to both MHC class I- and class II-restricted responses, which together are required for effector tumor immunity. Thus the cross-presentation pathway accessed by antigens acquired endocytically through Fc receptors links humoral and cellular immunity. These data suggest that administration of antitumor antibodies may enhance tumor-specific T cell responses in vivo and provide the rationale for Fc receptor targeting in vaccine development.
Rafiq
Khadija
K
Department of Medicine and Microbiology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Bergtold
Amy
A
Clynes
Raphael
R
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007116:Immunization, Passive; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017455:Receptors, IgE; D010047:Ovalbumin