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

H Liu; L Francis; LF Dagley; SA Cobbold; AI Webb; D Komander; JA Villadangos; JD Mintern

Journal article

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

H Liu, L Francis, LF Dagley, SA Cobbold, AI Webb, D Komander, JA Villadangos, JD Mintern

Scientific Reports | Published : 2025

DOI: 10.1038/s41598-025-25817-4

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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 ..

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