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U.S.A."],"published-print":{"date-parts":[[2025,5,27]]},"abstract":"<jats:p>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 cells during immune responses. The turnover of surface pMHC-II on antigen-presenting cells (APCs) is controlled by ubiquitin-mediated degradation of pMHC-II by the E3 ubiquitin ligase March-I. To study March-I protein expression, we have generated a mouse in which a V5 epitope-tag was knocked-in to the endogenous March-I gene, thereby allowing us to follow the fate of March-I using high-affinity anti-V5 antibodies. Quantitative analysis revealed that resting spleen DCs and B cells express only ~500 and 125 March-I molecules\/cell, respectively. Endogenous March-I protein has a very short half-life in DCs and March-I mRNA, March-I protein, and MHC-II ubiquitination are rapidly terminated upon activation of both DCs and B cells. Like March-I, CD83 is a known regulator of MHC-II expression in APCs and we also show that CD83 suppresses endogenous March-I-dependent MHC-II ubiquitination, endocytosis, and degradation in mouse spleen DCs. Thus, our study reveals molecular mechanisms for both March-I- and CD83-dependent regulation of MHC-II expression in APCs.<\/jats:p>","DOI":"10.1073\/pnas.2504077122","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T13:32:58Z","timestamp":1747834378000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["CD83 suppresses endogenous March-I-dependent MHC class II ubiquitination, endocytosis, and degradation"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0958-5627","authenticated-orcid":false,"given":"Sunil","family":"Kaul","sequence":"first","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, National Institutes of Health","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson B.","family":"Cole","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, 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