Analysis of E3 ubiquitin-protein ligases in antigen-specific CD4(+) T cells during tolerance and priming

Peripheral tolerance plays an important role in preventing T lymphocyte responses to self or harmless antigens. One of the mechanisms that contributes to this form of tolerance is anergy, which is characterized by a lack of proliferation and IL-2 production by T cells in response to antigenic challenge. The acquisition of the anergic phenotype is an active process, with negative regulators of T cell signaling being induced. Among these are the E3 ubiquitin-protein ligases which recognize target proteins for ubiquitination and catalyze the transfer of ubiquitin to them, directing them to the proteasome or to the endosome-lysosomal pathway, and hence down-regulating their activity.