CD83 suppresses endogenous March-I-dependent MHC class II ubiquitination, endocytosis, and degradation

• DOI: 10.1073/pnas.2504077122
• Publication Date: 2025-05-21T17:32:58Z
• Authors: Sunil Kaul; Nelson B. Cole; Joanna Bandola-Simon; Ying Lu; Elena Tondini; Even Walseng; Paul A. Roche
• Keywords: MHC restriction

MHC class II glycoproteins (MHC-II) bind peptides derived from exogenous antigens and dendritic cells (DCs) present these peptide MHC-II (pMHC-II) complexes to antigen-specific CD4 T during immune responses. The turnover of surface pMHC-II on antigen-presenting (APCs) is controlled by ubiquitin-mediated degradation the E3 ubiquitin ligase March-I. To study March-I protein expression, we have generated a mouse in which V5 epitope-tag was knocked-in endogenous gene, thereby allowing us follow fate using high-affinity anti-V5 antibodies. Quantitative analysis revealed that resting spleen DCs B express only ~500 125 molecules/cell, respectively. Endogenous has very short half-life mRNA, protein, ubiquitination are rapidly terminated upon activation both cells. Like March-I, CD83 known regulator expression APCs also show suppresses March-I-dependent ubiquitination, endocytosis, DCs. Thus, our reveals molecular mechanisms for March-I- CD83-dependent regulation APCs.