Mapping of the autophagosomal degradome identifies IL-7Rα as key cargo in proliferating CD4+ T-cells
Zhou, D.; Borsa, M.; Puleston, D. J.; Zellner, S.; Capera, J.; Sanderson, S.; Jostins, L.; Behrends, C.; Alsaleh, G.; Simon, A. K.
Show abstract
CD4+ T cells orchestrate both humoral and cytotoxic immune responses. While it is known that CD4+ T cell proliferation relies on autophagy, direct identification of the autophagosomal cargo involved is still missing. Here, we created a transgenic mouse model, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell by LC3 proximity labelling. IL-7R, a cytokine receptor mostly found in naive and memory T cells, was reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy showed increased IL-7R surface expression, while no defect in internalisation was observed. Mechanistically, excessive surface IL-7R sequestrates the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. This study provides proof-of-principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagys contribution to healthy physiology and disease.
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