title: Selective autophagy regulates T cell activation.
abstract: T cells are essential for defense of the host against invading pathogens. Antigen activation of the T cell receptor (TCR) is required for generation of an adaptive immune response. Several groups have observed that blocking autophagy augments T cell activation, but the molecular basis of this finding has remained elusive. The adaptor protein BCL10 transmits activating signals from the TCR to NFKB1-RELA/NFκB, a transcription factor that is critical for T cell proliferation and function. We recently reported that a TCR-dependent autophagy mechanism selectively targets and degrades BCL10. We found that BCL10 autophagy requires BCL10 K63-polyubiquitination and subsequent binding to the autophagy adaptor SQSTM1/p62. Blocking either one of these processes inhibits BCL10 degradation. Protecting BCL10 from autophagic degradation, either by pharmacological or genetic inhibition of autophagy, results in increased activation of NFKB1-RELA. By demonstrating the mechanism of autophagic uptake and degradation of BCL10, our study has revealed a key mechanism by which selective autophagy controls T cell activation. Here, we discuss the implications of our findings and explore possible directions for future research.
authors.affiliation: Department of Microbiology and Immunology, Center for Neuroscience and Regenerative Medicine, Uniformed Services University, Bethesda, MD, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Paul
authors.forename: Brian C
authors.initials: BC
authors.lastname: Schaefer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing