Cross-presentation by intercellular peptide transfer through gap junctions

Abstract

Major histocompatibility complex (MHC) class I molecules present peptides that are derived from endogenous proteins. These antigens can also be transferred to professional antigen-presenting cells in a process called cross-presentation, which precedes initiation of a proper T-cell response; but exactly how they do this is unclear. We tested whether peptides can be transferred directly from the cytoplasm of one cell into the cytoplasm of its neighbour through gap junctions. Here we show that peptides with a relative molecular mass of up to approximately 1,800 diffuse intercellularly through gap junctions unless a three-dimensional structure is imposed. This intercellular peptide transfer causes cytotoxic T-cell recognition of adjacent, innocent bystander cells as well as activated monocytes. Gap-junction-mediated peptide transfer is restricted to a few coupling cells owing to the high cytosolic peptidase activity. We present a mechanism of antigen acquisition for cross-presentation that couples the antigen presentation system of two adjacent cells and is lost in most tumours: gap-junction-mediated intercellular peptide coupling for presentation by bystander MHC class I molecules and transfer to professional antigen presenting cells for cross-priming.

B Cells Drive Early T Cell Autoimmunity In Vivo prior to Dendritic Cell-Mediated Autoantigen Presentation

“…A second mechanism that could explain our observations is the by the direct transfer of Ag between B cells and DCs. The latter mechanism has been supported by prior studies illustrating several mechanisms by which the transfer of Ag may occur between APC subsets (42)(43)(44)(45)). Antigenic peptides have been known to be exchanged between APCs via cell-to-cell contact or via gap junctions between cells (42).…”

Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus

“…A critical period of tracer loading is necessary to achieve reproducible steady-state conditions of tracer spread [20 Recent evidence suggests that large linear molecules, like polypeptides and siRNA, might ''wiggle through'' gap junctions formed by Cx43, to control gene expression and other cellular functions (27,28). Using complementary genetic approaches, we demonstrate that RG-like cells in the postnatal DG predominantly express Cx43 and, at a lower extent, Cx30 and Cx26.…”

Interferon‐β therapy reduces CD4+ and CD8+ T‐cell reactivity in multiple sclerosis

“…45 Other APC that might be of relevance for the stimulation of CD8 + T cells in PBMC cultures comprise monocytes, B cells, and cd T cells. [46][47][48] Although CD4 + and CD8 + T cells from both healthy donors and MS patients responded to MOG, these cells had different functional characteristics (Fig. 7).…”