A Novel Pathway of Alloantigen Presentation by Dendritic Cells

Abstract

In the context of transplantation, dendritic cells (DCs) can sensitize alloreactive T cells via two pathways. The direct pathway is initiated by donor DCs presenting intact donor MHC molecules. The indirect pathway results from recipient DCs processing and presenting donor MHC as peptide. This simple dichotomy suggests that T cells with direct and indirect allospecificity cannot cross-regulate each other because distinct APCs are involved. In this study we describe a third, semidirect pathway of MHC alloantigen presentation by DCs that challenges this conclusion. Mouse DCs, when cocultured with allogeneic DCs or endothelial cells, acquired substantial levels of class I and class II MHC:peptide complexes in a temperature- and energy-dependent manner. Most importantly, DCs acquired allogeneic MHC in vivo upon migration to regional lymph nodes. The acquired MHC molecules were detected by Ab staining and induced proliferation of Ag-specific T cells in vitro. These data suggest that recipient DCs, due to acquisition of donor MHC molecules, may link T cells with direct and indirect allospecificity.

Acquisition of MHC:Peptide Complexes by Dendritic Cells Contributes to the Generation of Antiviral CD8+ T Cell Immunity In Vivo

“…Alternatively, MHC class I:peptide complexes may be transferred through acquisition of plasma membrane from living or dying cells (40,41). Regardless of the mechanism involved, what is evident from our earlier in vitro data, and that of others, and also the data presented in this work, is that transferred MHC class I:peptide complexes are capable of activating Ag-specific CD8 + T cells (10,11,15,42).…”

CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL

“…One possibility would be that parenchymal cells acquire sufficient soluble ␤2M, or even intact MHCI contained in exosomes derived from wt hematopoietic cells, to permit direct cytolytic damage. [24][25][26][27] Alternatively, local release of inflammatory mediators, including cytokines and perforin/ granzymes, by CD8 ϩ T cells reacting with host antigen-bearing MHCI ϩ donor APCs may injure bystander MHCI Ϫ tissues. Either effect could be potentiated by underlying damage from irradiation, which disproportionately affects the ears.…”

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…In addition, γδ T cells have been shown to capture the membrane fragments from the tumor cells, such as Daudi cells (a B-lymphoblastoid cell line, derived from Burkitt's lymphoma) (34). Similarly, dendritic cells (DCs) have been shown to transfer the captured allogenic MHC class I and class II proteins in vivo, during transplantation (35,36).…”