Selective Autophagy of the Adaptor Protein BcI10 Modulates T Cell Receptor Activation of NF-κB

The adaptor protein BcI10 is a critically important mediator of T cell receptor (TCR)-to-NF-kappa B signaling. BcI10 degradation is a poorly understood biological phenomenon suggested to reduce TCR activation of NF-kappa B. Here we have shown that TCR engagement triggers the degradation of BcI10 in primary effector T cells but not in naive T cells. TCR engagement promoted K63 polyubiquitination of BcI10, causing BcI10 association with the autophagy adaptor p62. Paradoxically, p62 binding was required for both BcI10 signaling to NF-kappa B and gradual degradation of BcI10 by autophagy. BcI10 autophagy was highly selective, as shown by the fact that it spared Malt1, a direct BcI10 binding partner. Blockade of BcI10 autophagy enhanced TCR activation of NF-kappa B. Together, these data demonstrate that selective autophagy of BcI10 is a pathway-intrinsic homeostatic mechanism that modulates TCR signaling to NF-kappa B in effector I cells. This homeostatic process may protect T cells from adverse consequences of unrestrained NF-kappa B activation, such as cellular senescence.