Autophagy and adaptive immunity

Abstract

Summary Autophagy plays an important role in maintaining intracellular homeostasis by promoting the transit of cytoplasmic material, such as proteins, organelles and pathogens, for degradation within acidic organelles. Yet, in immune cells, autophagy pathways serve an additional role in facilitating intracellular surveillance for pathogens and changes in self. Autophagy pathways can modulate key steps in the development of innate and adaptive immunity. In terms of adaptive immunity, autophagy regulates the development and survival of lymphocytes as well as the modulation of antigen processing and presentation. Specialized forms of autophagy may be induced by some viral pathogens, providing a novel route for major histocompatibility complex (MHC) class I antigen presentation and enhanced CD8+ T‐cell responses. Autophagy induction in target cells also increases their potential to serve as immunogens for dendritic cell cross‐presentation to CD8+ T cells. The requirement for autophagy in MHC class II presentation of cytoplasmic and nuclear antigens is well established, yet recent studies also point to a critical role for autophagy in modulating CD4+ T‐cell responses to phagocytosed pathogens. Autophagy pathways can also modulate the selection and survival of some CD4+ T cells in the thymus. However, much still remains to be learned mechanistically with respect to how autophagy and autophagy‐linked genes regulate pathogen recognition and antigen presentation, as well as the development and survival of immune cells.

Molecular mimicry of MAGE-A6 andMycoplasma penetransHF-2 epitopes in the induction of antitumor CD8+T-cell responses

“…[7][8][9] In particular, Type-1 helper T-cell responses -distinguishable by virtue of interferon g (IFNg) expressionhave been shown to facilitate the cross-presentation of tumorassociated antigens (TAAs) by appropriately "licensing" host antigen presenting cells (APCs) and allowing for longitudinal diversification in the evolving antitumor T-cell repertoire. 10,11 These studies support the therapeutic need to induce both CD8 C and CD4…”

Autophagy: for better or for worse

“…Second, autophagy contributes to major histocompatibility complex (MHC) class I and II antigen presentation. Molecules captured by autophagosomes are delivered to the endosomal compartment, where antigens are proteolytically processed and loaded onto the MHC class I and II molecules for presentation to CD8 + and CD4 + T-cells, respectively [114]. For example, during herpes simplex virus (HSV-1) infection, autophagy facilitates presentation of HSV-1 antigens on MHC class I molecules, and mice with Atg5-deficient dendritic cells show impaired CD4 + T-cell priming upon HSV-1 infection [115,116].…”

Mycobacterial Induction of Autophagy Varies by Species and Occurs Independently of Mammalian Target of Rapamycin Inhibition

“…Autophagic elimination of intracellular mycobacteria occurs upon fusion of bacteria housed within LC3B-II-positive autophagsomes with lysosomes, thereby exposing mycobacteria to reduced pH, proteases, and a customized formulation of neo-antimicrobial peptides (6,9). The digestion and killing of bacteria in this fashion liberates antigenic epitopes that can be presented on the cell surface in the context of major histocompatibility class II and I protein complexes for detection by antigen-specific CD4 ϩ and CD8 ϩ T lymphocytes (4,11). As expected, the infection of dendritic cells with recombinant BCG and treatment with rapamycin has been shown to enhance the immunogenicity of mycobacterial antigens (12).…”