Mouse Endothelial Cells Cross-Present Lymphocyte-Derived Antigen on Class I MHC via a TAP1- and Proteasome-Dependent Pathway

Abstract

In vivo studies suggest that vascular endothelial cells (ECs) can acquire and cross-present exogenous Ag on MHC-I but the cellular mechanisms underlying this observation remain unknown. We tested whether primary female mouse aortic ECs could cross-present exogenous male Ag to the T cell hybridoma, MHH, specific for HYUty plus Db. MHC-I-deficient male spleen cells provided a source of male Ag that could not directly stimulate the MHH cells. Addition of male but not female MHC-I-deficient spleen cells to wild-type syngeneic female EC induced MHH stimulation, demonstrating EC cross-presentation. Lactacystin treatment of the donor male MHC-I-deficient spleen cells, to inhibit proteasome function, markedly enhanced EC cross-presentation showing that the process is most efficient for intact proteins rather than degraded peptide fragments. Additional experiments revealed that this EC Ag-processing pathway is both proteasome and TAP1 dependent. These studies demonstrate that cultured murine aortic ECs can process and present MHC-I-restricted Ag derived from a separate, live cell, and they offer insight into the molecular requirements involved in this EC Ag presentation process. Through this pathway, ECs expressing cross-presented peptides can participate in the effector phase of T cell-mediated inflammatory responses such as autoimmunity, anti-tumor immunity, and transplant rejection.

Steady-State Antigen Scavenging, Cross-Presentation, and CD8+ T Cell Priming: A New Role for Lymphatic Endothelial Cells

“…As described for other murine stromal cells, such as LSECs (14,48), aortic endothelial cells (49), and thymic stromal cells (50), we found that the TAP1-dependent transport of cytoplasmic peptides into the ER (Fig. 2D) and ER-golgi trafficking (Fig.…”

Targeting the Gut Vascular Endothelium Induces Gut Effector CD8 T Cell Responses Via Cross-Presentation by Dendritic Cells

“…Mouse vascularized cardiac allografts can be acutely rejected via direct recognition of foreign class I molecules by CD8 T cells, even when the graft hemopoietic cells are syngeneic with the host's (36). In vitro experiments demonstrated that insulinspecific CD8 cells directly recognized pancreatic endothelial cells in islet organ cultures (37) and mouse endothelial cells crosspresent Ag to CD8 T cell hybridomas via a TAP1-and proteasome-dependent pathway (38). However, it is still an unresolved issue whether endothelial cells can activate naive T cells in vivo.…”

Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties

“…3,8 Although cross-presentation is a characteristic of DCs 9 and macrophages, 10 cross-presentation can be performed, although less efficiently, by other cell types such as neutrophils, 11 B cells, 12 and endothelial cells. 13 Bone marrow mesenchymal stromal cells (MSCs), which are nonhematopoietic progenitor cells, possess, along with their ability to differentiate into several mesenchymal tissue lineages, the capacity to behave as APCs. More precisely, once stimulated with interferon (IFN)-␥, these cells can uptake, process, and present exogenous antigens through their MHC class II molecules, leading to the activation of naive CD4 ϩ T cells in vitro and in vivo.…”