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choriomeningitis virus infection [ 10]. Autophagy activity may increase at the peak of CD8+ Teff responses, suggesting that autophagy could play an important role during the transition from Teff to T memory (Tmem) CD8+ cells [10]. Both studies also linked defects in CD8+ T cell memory formation to failure to induce metabolic switches, namely the upregulation of fatty acid oxidation, which is key to CD8+ T cell memory formation [10, 52, 84].

gure 1. Mechanism of autophagy in T cells

TCR-induced expression of IL-2 leads to activation of the IL-2 receptor (IL-2r),which leads to the activation of autophagy in T helper cells in a JAK1.3-dependent manner. The initiation of autophagy and formation of the limiting membrane and thenphagophore are driven by

two complexes: the ULK-complex—ULK/FIP200/Atg101/Atg13; and the Beclin-1/Vps34 complex (class III phosphatidylinositol-3-kinase complex (PI3KC3) containing Beclin-1,

Vps34,Vps15,Atg14 and Ambra1). Two cascades of ubiquitin-like conjugation systems

regulate the elongation and maturation of the denovo formed double-membrane vesicle to form the autophagosome, which eventually fuses with the lysosome to degrade cargo. The lipidation of LC3 to PE allows association with the membranes of the autophagosome. This allows specific substrates to be targeted to the autophagosome by interaction with LC3 via LC3-interacting motifs as well as autophagic cargo receptors with LC3-interacting regions. The specific sequestration and degradation of substrates complements in-bulk mechanisms of degradation of organelles, macromolecules (i.e. proteins, lipids, glycogen),ａnd other

cellular components.