Immune surveillance of intracellular pathogens via autophagy

Abstract

MHC class II molecules are thought to present peptides derived from extracellular proteins to CD4 þ T cells, which are important mediators of adaptive immunity to infections. In contrast, autophagy delivers constitutively cytosolic material for lysosomal degradation and has so far been recognized as an efficient mechanism of innate immunity against bacteria and viruses. Recent studies, however, link these two pathways and suggest that intracellular cytosolic and nuclear antigens are processed for MHC class II presentation after autophagy.

Modified Vaccinia Virus Ankara-Infected Dendritic Cells Present CD4 + T-Cell Epitopes by Endogenous Major Histocompatibility Complex Class II Presentation Pathways

“…To date, two mechanistically distinct antigen presentation pathways have been identified for CD4 ϩ T-cell activation. Apart from the classical pathway with presentation of phagocytosed exogenous antigens, there is emerging evidence for endogenous MHCII presentation by processing of cytosolic antigens in different infection models as well as for self and tumor antigens (9). Several studies have investigated a possible role of endogenous MHCII presentation for antigens expressed by vaccinia viral vectors, but the results were quite inconsistent and may reflect differences in the vector backbone, choice of antigen, and detection systems used.…”

“…The first hint that intracellular antigens are loaded on MHCII was obtained by sequence analysis of peptides bound to MHCII, showing that the majority of those ligands were derived from endogenous proteins (6). Since then, endogenous MHCII presentation has been shown to occur not only for self-antigens to mediate tolerance (7,8) but also for viral antigens (like measles virus ma-trix and nucleocapsid protein, influenza A hemagglutinin, HCV core protein, and EBV nuclear antigen 1) as well as tumor antigens (such as MUC-1 and mutated CDC27) to broaden the spectrum of immunogenic MHCII ligands (9). Moreover, classical presentation seems to play a relatively minor role, while alternative presentation pathways seem to contribute substantially to MHCII peptide presentation (10).…”

“…Different pathways have been suggested to be involved in MHCII presentation of intracellular antigens (9). First, secreted or transmembrane proteins can be translocated by the Sec61 translocon into the endoplasmic reticulum (ER), where they associate with MHCII and are further guided to endosomal compartments (11).…”

Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein

“…For example, autophagy defends cells against invasive bacteria and viruses [71,[74][75][76], and is involved in major histocompatibility complex II antigen presentation [77,78]. Similarly, autophagy plays a role in innate immunity in plants.…”

How many ways to die? How many different models of cell death?

“…RAK: In several reviews published in this issue of Cell Death Differentiation, several manuscripts describe autophagy in detail, [2][3][4][5][6][7][8][9][10] while Lippens et al 11 contrast two distinct forms of death, apoptosis and cornification in the skin, see also for review. 12 Although these two processes may appear to have superficial similarities, their detailed mechanisms are largely different.…”