MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway

作者：Wilson Kayla R; Liu Haiyin; Healey Geraldine; Vuong Vivian; Ishido Satoshi; Herold Marco J; Villadangos Jose A^*; Mintern Justine D^*

来源：PLos One, 2018, 13(7): e0200540.

DOI：10.1371/journal.pone.0200540

Major histocompatibility complex class II (MHC II) expression and turn-over are regulated via its ubiquitination by the membrane associated RING-CH 1 (MARCH1) E3 ligase. Unexpectedly, we show that MHC II ubiquitination also impacts MHC I. Lack of MARCH1 in B cells and dendritic cells (DCs) resulted in a significant reduction in surface MHC I expression. This decrease was not directly caused by changes in MARCH1 ubiquitination of MHC I but indirectly by altered MHC II trafficking in the absence of its ubiquitination. Deletion of MHC II in March 1(-/-) cells restored normal MHC I surface expression and replacement of wild type MHC II by a variant that could not be ubiquitinated caused a reduction in MHC I expression. Furthermore, these cells displayed inefficient presentation of peptide and protein antigen via MHC I to CD8(+) T cells. In summary, we describe an unexpected intersection between MHC I and MHC II such that the surface expression of both molecules are indirectly and directly regulated by MARCH1 ubiquitination, respectively.

• 出版日期2018-7-12
• 单位河北医科大学