Dendritic Cells Acquire Antigens from Live Cells for Cross-Presentation to CTL

Abstract

Dendritic cells (DC) can readily capture Ag from dead and dying cells for presentation to MHC class I-restricted CTL. We now show by using a primate model that DC also acquire Ag from healthy cells, including other DC. Coculture assays showed that fluorescently labeled plasma membrane was rapidly and efficiently transferred between DC, and transfer of intracellular proteins was observed to a lesser extent. Acquisition of labeled plasma membrane and intracellular protein was cell contact-dependent and was primarily a function of immature DC, whereas both immature and CD40L-matured DC could serve as donors. Moreover, immature DC could acquire labeled plasma membrane and intracellular proteins from a wide range of hemopoietic cells, including macrophages, B cells, and activated T cells. Notably, macrophages, which readily phagocytose apoptotic bodies, were very inefficient at acquiring labeled plasma membrane and intracellular proteins from other live macrophages or DC. With live-cell imaging techniques, we demonstrate that individual DC physically extract plasma membrane from other DC, generating endocytic vesicles of up to 1 microm in diameter. Finally, DC but not macrophages acquired an endogenous melanoma Ag expressed by live DC and cross-presented Ag to MHC class I-restricted CTL, demonstrating the immunological relevance of our finding. These data show for the first time that DC readily acquire Ag from other live cells. We suggest that Ag acquisition from live cells may provide a novel mechanism whereby DC can present Ag in the absence of direct infection, and may serve to expand and regulate the immune response in vivo.

Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells—A Key Role for Heat-Shock Protein 70 and Receptor CD91

“…Furthermore, DCs can acquire antigen from live cells for antigen cross-presentation in both tumor and viral settings (44)(45)(46). In the latter, while apoptosis is inhibited by the virus, Hsp70 expression is significantly upregulated (47).…”

The Kinetics of In Vivo Priming of CD4 and CD8 T Cells by Dendritic/Tumor Fusion Cells in MUC1-Transgenic Mice

“…DC or Langerhans cells in the epidermis are thought to capture exogenous Ags, migrate into draining lymph nodes (DLN), and reside in the T cell parafollicular and paracortical zones. The initial priming of T cells takes place in the DLN (9,20).…”

T cell activation correlates with an increasedproportion of antigen among the materials acquiredfrom target cells

“…Trogocytosis has been recorded with every lymphocyte type, and its proposed role(s) differ depending on the cell type. For instance, trogocytosis as performed by DC is involved in affinity maturation of T cells [28], antigen capture [29,30] and cross-presentation [31]. As far as T cells are concerned, the capture of pepMHC complexes has been proposed to control CTL responses negatively by means of fratricide [18,32] (explaining, at least in part, the phenomenon of CTL exhaustion reported to occur at high antigen loads [33][34][35]), tolerance induction [36] or immunoregulation [22].…”