Major histocompatibility class II in murine antigen presenting cells is modified with a branched K63 and K11-linked ubiquitin chain.

ABSTRACT: Major histocompatibility class II (MHC II) is critical for adaptive immunity. MHC II intracellular trafficking and degradation is regulated by ubiquitination. Poly-ubiquitination (Ub) of MHC II directs it away from the plasma membrane and is a critical determinant of MHC II turnover. The MHC II Ub chain has not been characterized. Here, we describe the poly-Ub chain associated with MHC II in primary murine antigen presenting cells; conventional dendritic cells (cDCs) and B cells. Analysis was conducted for endogenous murine MHC II isoforms H2-A and H2-E immunoprecipitated from primary cells. We show that ubiquitination of both I-A and I-E expressed by cDCs and B cells is dependent on the E3 Ub ligase MARCH1. Using mass spectrometry Ub chain linkage analysis and innovative Ub "clipping" pro

SUBMITTER: Liu H 

PROVIDER: S-EPMC12647164 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature