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.

Keywords: :

• Bcl10
• LC3
• NF-kappaB
• SQSTM1
• T cell
• TCR
• p62
• proteasome
• signal transduction
• ubiquitin

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Acknowledgments

Supported by grants from the National Institutes of Health (AI057481 to B.C.S.), the Center for Neuroscience and Regenerative Medicine (CNRM) (to B.C.S.), and a predoctoral fellowship (to S.P.) from the American Heart Association.