Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells.

Zhenzhen Liu,Paul A Roche

doi:10.3389/fphys.2015.00001

Abstract

Dendritic cells (DCs) are outstanding antigen presenting cells (APCs) due to their robust ability to internalize extracellular antigens using endocytic processes such as receptor-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis mediates the non-specific uptake of soluble antigens and occurs in DCs constitutively. Macropinocytosis plays a key role in DC-mediated antigen presentation to T cells against pathogens and the efficiency of macropinocytosis in antigen capture is regulated during the process of DC maturation. Here, we review the methods to study macropinocytosis, describe our current knowledge of the regulatory mechanisms of antigen uptake via macropinocytosis and the intracellular trafficking route followed by macropinocytosed antigens, and discuss the significance of macropinocytosis for DC function.

Highlights

Dendritic cells (DCs) are the most accomplished of professional antigen presenting cells (APCs) and are responsible for initiating T cell responses against pathogens (Villadangos and Schnorrer, 2007)
Besides stimulating distinct classes of T cells, it is generally true that MHC-I and MHC-II differ in the sites of intracellular antigenic peptide generation
MHC-Idestined peptides are generated by cytosolic proteolysis of endogenous proteins and foreign antigens, and these peptides are translocated into the endoplasmic reticulum for binding to nascent MHC-I

Summary

INTRODUCTION

Dendritic cells (DCs) are the most accomplished of professional antigen presenting cells (APCs) and are responsible for initiating T cell responses against pathogens (Villadangos and Schnorrer, 2007). DCs express peptide fragments of degraded foreign antigens on their surface bound to MHC glycoproteins, molecules that function as “display platforms” presenting peptide-fragments for recognition by antigen-specific T cells (Blum et al, 2013). DCs concurrently mature and migrate to secondary lymphoid organs (such as lymph nodes) where their surface pMHC-I and pMHC-II present antigenic peptides to T cells to initiate antigen-specific adaptive immune responses. Receptor-mediated endocytosis requires antigen (usually small soluble molecules) binding to a variety of receptors on DCs (most notably lectins, Fc receptors, and complement receptors) that are internalized in clathrin-coated and non-clathrin-coated vesicles. Like receptor-mediated endocytosis, phagocytosis is usually initiated by antigen binding to DC surface “receptors,” DCs can internalize large particles (such as antigen-coated latex beads) by non-specific phagocytosis. Macropinocytosis occurs constitutively in DCs and DCs generated in vitro from mouse bone marrow (BMDC) can internalize approximately 2 fL/cell/min (Norbury et al, 1997), thereby providing these cells with a robust mechanism of non-specific foreign antigen uptake

METHODS

CONCLUSION