[HTML][HTML] Immune complex–mediated antigen presentation induces tumor immunity

K Rafiq, A Bergtold, R Clynes - The Journal of clinical …, 2002 - Am Soc Clin Investig
K Rafiq, A Bergtold, R Clynes
The Journal of clinical investigation, 2002Am Soc Clin Investig
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 FcγRγ–/–
DCs loaded with ovalbumin-containing immune complexes. Tumor protection was …
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 FcγRγ–/–DCs loaded with ovalbumin-containing immune complexes. Tumor protection was eliminated when immune complex–loaded DCs lacked β 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.
The Journal of Clinical Investigation