The Relative Efficiency of Acquisition of MHC:Peptide Complexes and Cross-Presentation Depends on Dendritic Cell Type

Abstract

Intercellular exchange of MHC molecules has been reported between many cells, including professional and nonprofessional APCs. This phenomenon may contribute to T cell immunity to pathogens. In this study, we addressed whether the transfer of MHC class I:peptide complexes between cells plays a role in T cell responses and compare this to conventional cross-presentation. We observed that dsRNA-matured bone marrow-derived dendritic cells (BMDCs) acquired peptide:MHC complexes from other BMDCs either pulsed with OVA257–264 peptide, soluble OVA, or infected with a recombinant adenovirus expressing OVA. In addition, BMDCs were capable of acquiring MHC:peptide complexes from epithelial cells. Spleen-derived CD8α+ and CD8α− dendritic cells (DCs) also acquired MHC:peptide complexes from BMDCs pulsed with OVA257–264 peptide. However, the efficiency of acquisition by these ex vivo derived DCs is much lower than acquisition by BMDC. In all cases, the acquired MHC:peptide complexes were functional in that they induced Ag-specific CD8+ T cell proliferation. The efficiency of MHC transfer was compared with cross-presentation for splenic CD8α+ and CD8α− as well as BMDCs. CD8α+ DCs were more efficient at inducing T cell proliferation when they acquired Ag via cross-presentation, the opposite was observed for BMDCs and splenic CD8α− DCs. We conclude from these observations that the relative efficiency of MHC transfer vs cross-presentation differs markedly between different DC subsets.

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

“…Likewise, we have observed that DCs can acquire MHC:peptide complexes from epithelial cells in vitro (10). This suggested that DCs trafficking through a virus-infected tissue could de facto acquire Ag in the form of preformed MHC class I:peptide complexes from virally infected parenchymal cells and subsequently present the acquired MHC: peptide complexes to T cells in lymph nodes (LNs) (10). Consistent with this hypothesis, Wakim and Bevan (11) recently provided compelling evidence that virus-infected parenchymal cells cross-dress DC with peptide-loaded MHC class I and drive T cell proliferation in vivo.…”

“…Furthermore, the transferred MHC:OVA peptide complexes were functional in that they stimulated OVA-specific CD8 + T cell proliferation and IL-2 production (9). Likewise, we have observed that DCs can acquire MHC:peptide complexes from epithelial cells in vitro (10). This suggested that DCs trafficking through a virus-infected tissue could de facto acquire Ag in the form of preformed MHC class I:peptide complexes from virally infected parenchymal cells and subsequently present the acquired MHC: peptide complexes to T cells in lymph nodes (LNs) (10).…”

“…Additionally, there is indirect presentation in which Ag is transferred from live or apoptotic virus-infected cells to uninfected APC and cytosolic peptide cross-presented by the MHC class I molecules expressed by the recipient APC (2)(3)(4)(5)(6)(7)(8). Recently, a third mechanism known as cross-dressing has been proposed to contribute to antiviral immunity, whereby an uninfected APC acquires pre-existing MHC class I:peptide molecules from a virus-infected cell (9)(10)(11). In support of such a role, we, and others, have shown that MHC class I:peptide complexes can be acquired by immature and mature dendritic cells (DCs) both in vitro and in vivo (10)(11)(12)(13)(14)(15).…”

“…Recently, a third mechanism known as cross-dressing has been proposed to contribute to antiviral immunity, whereby an uninfected APC acquires pre-existing MHC class I:peptide molecules from a virus-infected cell (9)(10)(11). In support of such a role, we, and others, have shown that MHC class I:peptide complexes can be acquired by immature and mature dendritic cells (DCs) both in vitro and in vivo (10)(11)(12)(13)(14)(15). Furthermore, the transferred MHC:OVA peptide complexes were functional in that they stimulated OVA-specific CD8 + T cell proliferation and IL-2 production (9).…”

“…Such a scenario for multiple Ag-processing pathways activating naive CD8 + T cells in vivo is not inconceivable (16). Evidence that this may occur comes from our previous observations that ex vivo splenic CD8a + and CD8a 2 DC subsets can acquire MHC:peptide complexes from bone marrow-derived DCs (BM-DCs) in vitro and stimulate Ag-specific T cells (10). Likewise, Qu et al (14) reported that migratory MHC class Iexpressing monocyte-derived DCs transfer intact MHC class I: peptide complexes to MHC class I-deficient splenic DCs.…”