Innate and adaptive immunity through autophagy

Abstract

Major histocompatibility complex (MHC) class II molecules present products of lysosomal proteolysis to CD4+ T cells. Although extracellular antigen uptake is considered to be the main source of MHC class II ligands, a few intracellular antigens, including the nuclear antigen 1 of the Epstein Barr Virus, have been described to gain access to MHC class II loading after macroautophagy. However, the general relevance and efficacy of this pathway is still debated. In addressing these questions, we could demonstrate constitutive autophagosome formation in MHC class II positive cells, including dendritic, B and epithelial cells. The autophagosomes continuously fused with multivesicular MHC class II‐loading compartments (MIICs). This pathway was of functional relevance, because targeting of the Influenza Matrix Protein 1 (MP1) to autophagosomes via fusion to the autophagosome‐associated protein Atg8/LC3 led to strongly enhanced MHC class II presentation to CD4+ T cell clones. The importance of this pathway is demonstrated by the fact that both DNA and RNA viruses inhibit the pathway, and might thereby escape immune control. We suggest that macroautophagy constitutively and efficiently delivers cytosolic proteins, like viral antigens, for MHC class II presentation and can be harnessed for improved helper T cell stimulation.This research is supported by the National Cancer Institute (R01 CA101741), the National Institute of Allergy and Infectious Disease (RFP‐NIH‐NIAID‐DAIDS‐BAA‐06‐19), the Beckman Foundation, the Sinsheimer Scholars Program and the Burroughs Wellcome Fund.