The ABCs of Antigen Presentation by Stromal Non-Professional Antigen-Presenting Cells.

Tom J Harryvan,Els M.E Verdegaal,Lukas J.A.C Hawinkels,Sabine De Lange

doi:10.3390/ijms23010137

Abstract

Professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, are known for their ability to present exogenous antigens to T cells. However, many other cell types, including endothelial cells, fibroblasts, and lymph node stromal cells, are also capable of presenting exogenous antigens to either CD8+ or CD4+ T cells via cross-presentation or major histocompatibility complex (MHC) class II-mediated presentation, respectively. Antigen presentation by these stromal nonprofessional APCs differentially affect T cell function, depending on the type of cells that present the antigen, as well as the local (inflammatory) micro-environment. It has been recently appreciated that nonprofessional APCs can, as such, orchestrate immunity against pathogens, tumor survival, or rejection, and aid in the progression of various auto-immune pathologies. Therefore, the interest for these nonprofessional APCs is growing as they might be an important target for enhancing various immunotherapies. In this review, the different nonprofessional APCs are discussed, as well as their functional consequences on the T cell response, with a focus on immuno-oncology.

Highlights

Antigen presentation is a crucial aspect in mounting an effective immune response against pathogens and tumors
Recent insights in stromal immunobiology [23,64,65] reveal an important role for regulation of the T cell response by different stromal cell types, but it is largely unknown how nonprofessional antigen presentation directly contributes to regulating T cell responses
The assessment of the differences between nonprofessional antigen-presenting cells (APCs) and professional APCs shows that the uptake and processing routes of exogenous antigens are generally similar, with notable exceptions for the antigen half-life and the expression of MHC class II (MHCII)

Summary

Introduction

Antigen presentation is a crucial aspect in mounting an effective immune response against pathogens and tumors. Detailed assessment revealed that this was not attributable to a difference in antigen processing capacity between professional and nonprofessional APCs, but rather to a difference in expression of co-stimulatory molecules These studies show that the exogenous antigen (cross)presentation machinery is present in a variety of fibroblasts and that the extent of T cell activation that subsequently occurs might not be a result of insufficient antigen processing but rather the absence of the appropriate co-stimulatory cues. As the expression of these co-stimulatory molecules is dynamic and strongly regulated via inflammatory mediators, such as IFNγ, it is conceivable that the capacity of fibroblasts (and other nonprofessional APCs) to mediate the T cell response depends on the (tumor) micro-environment in which the antigen presentation occurs. These cues can conditionally enhance fibroblast antigen-presenting abilities and/or alter the expression of co-stimulatory molecules that define the resulting T cell response

Lymph Node Stromal Cells

Endothelial Cells

Summary

Findings

Conclusions