Autophagy and Its Role in MHC-Mediated Antigen Presentation

Abstract

Intracellular degradation by autophagy plays a role in the maintenance of cellular homeostasis under normal conditions and during periods of cellular stress. Autophagy has also been implicated in several other cellular processes including immune recognition and responsiveness. More specifically, autophagy has been identified as a route by which cytoplasmic and nuclear Ag are delivered to MHC class II molecules for presentation to CD4+ T cells. Autophagy has also recently been implicated in MHC class I cross-presentation of tumor Ag and the activation of CD8+ T cells. This review discusses the role of autophagy in modulating MHC class I and class II Ag presentation as well as its implication in regulating autoimmunity and tolerance, tumor immunity, and host defense against intracellular pathogens.

Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells—A Key Role for Heat-Shock Protein 70 and Receptor CD91

“…We have not addressed directly whether Hsp70's role in this model lies mainly in antigen-chaperoning (33,38,39) or enhancing autophagy (40) or triggering DC maturation (41,42) with subsequent increase in T-cell stimulation. All of these known functions can be important and they likely play a synergistic role.…”

The Effect of Proteasome Inhibition on the Generation of the Human Leukocyte Antigen (HLA) Peptidome

“…The vacuolar/endolysosomal pathway was proposed as a significant, nonproteasomal degradation pathway for a variety of cytosolic and membranal proteins (64). The endolysosomal pathway was studied more for its involvement in producing the HLA class II peptidomes (reviewed in (16,17)) and for cross presentation of HLA class I peptides ((65), reviewed in (22, 66 -68)). Furthermore, although the proteasome was proposed as the main protease responsible for degradation of newly synthesized proteins, including DRiPs and SLiPs, autophagy and lysosomal proteolysis were mostly associated with degradation of long-lived, house-keeping proteins and whole organelles at the end of their functional lifecycles (64).…”

“…In contrast to the mostly cytoplasmic and ER production of the MHC class I peptidome, the class II peptidome is produced in a special compartment, associated with the endolysosome pathway (18 -20). This pathway is also thought to participate in the cross presentation of class I peptides, derived from proteins up-taken by professional antigen presenting cells (21), (reviewed in (15)(16)(17)22)). …”

MyD88 Interacts with Interferon Regulatory Factor (IRF) 3 and IRF7 in Atlantic Salmon (Salmo salar)

“…The autophagy is a mechanism for elimination of old or damaged organelles and insoluble proteins aggregates (61). In addition, autophagy has important immune functions because it is implicated in elimination of intracellular pathogens, the delivery of TLR ligands in endosomal compartments (62), and antigen presentation (63). TLR signaling is involved in the autophagy regulation both through MyD88-dependent and -independent mechanism(s) (64 -67), and it has been found that activation of macrophages and dendritic cells with TLR ligands results in formation of ALIS in which polyubiquitinated aggregates are directed by p62 to autophagosomes (32).…”