{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:32:54Z","timestamp":1790253174018,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2\u2212\/\u2212 mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-\u03b1, IL-1\u03b2, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-\u03baB activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing.<\/jats:p>","DOI":"10.4049\/jimmunol.0903003","type":"journal-article","created":{"date-parts":[[2010,3,12]],"date-time":"2010-03-12T21:10:31Z","timestamp":1268428231000},"page":"4115-4122","source":"Crossref","is-referenced-by-count":90,"title":["Unexpected Role for the Immunoproteasome Subunit LMP2 in Antiviral Humoral and Innate Immune Responses"],"prefix":"10.1093","volume":"184","author":[{"given":"Scott E","family":"Hensley","sequence":"first","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Zanker","sequence":"additional","affiliation":[{"name":"T Cell Laboratory, Melbourne Centre for Clinical Sciences, Ludwig Institute for Cancer Research, Austin Health , Heidelberg,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P","family":"Dolan","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"David","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather D","family":"Hickman","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan C","family":"Embry","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara N","family":"Skon","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie M","family":"Grebe","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Griffin","sequence":"additional","affiliation":[{"name":"William S. Rowe Division of Rheumatology, Cincinnati Children\u2019s Hospital Medical Center and University of Cincinnati College of Medicine , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisan","family":"Chen","sequence":"additional","affiliation":[{"name":"T Cell Laboratory, Melbourne Centre for Clinical Sciences, Ludwig Institute for Cancer Research, Austin Health , Heidelberg,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack R","family":"Bennink","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan W","family":"Yewdell","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,4,15]]},"reference":[{"key":"2026012808080675000_r1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0092-8674(94)90462-6","article-title":"Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class molecules.","volume":"78","author":"Rock","year":"1994","journal-title":"Cell"},{"key":"2026012808080675000_r2","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1074\/jbc.274.6.3363","article-title":"The sizes of peptides generated from protein by mammalian 26 and 20 S proteasomes. Implications for understanding the degradative mechanism and antigen presentation.","volume":"274","author":"Kisselev","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2026012808080675000_r3","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0092-8674(94)90482-0","article-title":"The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B.","volume":"78","author":"Palombella","year":"1994","journal-title":"Cell"},{"key":"2026012808080675000_r4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(00)00080-5","article-title":"Activation of a membrane-bound transcription factor by regulated ubiquitin\/proteasome-dependent processing.","volume":"102","author":"Hoppe","year":"2000","journal-title":"Cell"},{"key":"2026012808080675000_r5","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1126\/science.7725097","article-title":"Crystal structure of the 20S proteasome from the Archaeon T. acidophilum at 3.4 A resolution.","volume":"268","author":"L\u00f6we","year":"1995","journal-title":"Science"},{"key":"2026012808080675000_r6","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/jlb.56.5.571","article-title":"Role of proteasomes modified by interferon-gamma in antigen processing.","volume":"56","author":"Tanaka","year":"1994","journal-title":"J. Leukoc. Biol."},{"key":"2026012808080675000_r7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1600-065X.1998.tb01195.x","article-title":"The MHC class I ligand-generating system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28.","volume":"163","author":"Tanaka","year":"1998","journal-title":"Immunol. Rev."},{"key":"2026012808080675000_r8","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1128\/JVI.01779-06","article-title":"Role of immunoproteasome catalytic subunits in the immune response to hepatitis B virus.","volume":"81","author":"Robek","year":"2007","journal-title":"J. Virol."},{"key":"2026012808080675000_r9","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1128\/JVI.77.2.1227-1236.2003","article-title":"Searching for interferon-induced genes that inhibit hepatitis B virus replication in transgenic mouse hepatocytes.","volume":"77","author":"Wieland","year":"2003","journal-title":"J. Virol."},{"key":"2026012808080675000_r10","doi-asserted-by":"crossref","first-page":"6859","DOI":"10.4049\/jimmunol.167.12.6859","article-title":"Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver.","volume":"167","author":"Khan","year":"2001","journal-title":"J. Immunol."},{"key":"2026012808080675000_r11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1084\/jem.187.1.97","article-title":"Immunoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits.","volume":"187","author":"Griffin","year":"1998","journal-title":"J. Exp. Med."},{"key":"2026012808080675000_r12","doi-asserted-by":"crossref","first-page":"8970","DOI":"10.1073\/pnas.94.17.8970","article-title":"The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome.","volume":"94","author":"Groettrup","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808080675000_r13","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1006\/jmbi.2000.4185","article-title":"Different proteasome subtypes in a single tissue exhibit different enzymatic properties.","volume":"303","author":"Dahlmann","year":"2000","journal-title":"J. Mol. Biol."},{"key":"2026012808080675000_r14","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1074\/mcp.M700187-MCP200","article-title":"Mammalian proteasome subpopulations with distinct molecular compositions and proteolytic activities.","volume":"6","author":"Drews","year":"2007","journal-title":"Mol. Cell. Proteomics"},{"key":"2026012808080675000_r15","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1093\/emboj\/20.10.2357","article-title":"26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide.","volume":"20","author":"Cascio","year":"2001","journal-title":"EMBO J."},{"key":"2026012808080675000_r16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.coi.2003.11.004","article-title":"Proteasome and peptidase function in MHC-class-I-mediated antigen presentation.","volume":"16","author":"Kloetzel","year":"2004","journal-title":"Curr. Opin. Immunol."},{"key":"2026012808080675000_r17","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1084\/jem.193.11.1319","article-title":"Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens.","volume":"193","author":"Chen","year":"2001","journal-title":"J. Exp. Med."},{"key":"2026012808080675000_r18","doi-asserted-by":"crossref","first-page":"4075","DOI":"10.4049\/jimmunol.176.7.4075","article-title":"T cells lacking immunoproteasome subunits MECL-1 and LMP7 hyperproliferate in response to polyclonal mitogens.","volume":"176","author":"Caudill","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808080675000_r19","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1128\/IAI.01134-07","article-title":"The proteasome immunosubunit multicatalytic endopeptidase complex-like 1 is a T-cell-intrinsic factor influencing homeostatic expansion.","volume":"76","author":"Zaiss","year":"2008","journal-title":"Infect. Immun."},{"key":"2026012808080675000_r20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.0105-2896.2005.00309.x","article-title":"The seven dirty little secrets of major histocompatibility complex class I antigen processing.","volume":"207","author":"Yewdell","year":"2005","journal-title":"Immunol. Rev."},{"key":"2026012808080675000_r21","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.4049\/jimmunol.175.2.1153","article-title":"Immunoproteasome-deficient mice mount largely normal CD8+ T cell responses to lymphocytic choriomeningitis virus infection and DNA vaccination.","volume":"175","author":"Nussbaum","year":"2005","journal-title":"J. Immunol."},{"key":"2026012808080675000_r22","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/ni736","article-title":"Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.","volume":"2","author":"Asselin-Paturel","year":"2001","journal-title":"Nat. Immunol."},{"key":"2026012808080675000_r23","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1002\/(SICI)1521-4141(199912)29:12<4037::AID-IMMU4037>3.0.CO;2-T","article-title":"Dendritic cells up-regulate immunoproteasomes and the proteasome regulator PA28 during maturation.","volume":"29","author":"Macagno","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2026012808080675000_r24","doi-asserted-by":"crossref","first-page":"7680","DOI":"10.4049\/jimmunol.177.11.7680","article-title":"Immunoproteasome subunit deficiencies impact differentially on two immunodominant influenza virus-specific CD8+ T cell responses.","volume":"177","author":"Pang","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808080675000_r25","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/1074-7613(94)90043-4","article-title":"Altered peptidase and viral-specific T cell response in LMP2 mutant mice.","volume":"1","author":"Van Kaer","year":"1994","journal-title":"Immunity"},{"key":"2026012808080675000_r26","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1084\/jem.164.4.1114","article-title":"Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin.","volume":"164","author":"Scherle","year":"1986","journal-title":"J. Exp. Med."},{"key":"2026012808080675000_r27","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1084\/jem.20021745","article-title":"An early CD4+ T cell-dependent immunoglobulin A response to influenza infection in the absence of key cognate T-B interactions.","volume":"198","author":"Sangster","year":"2003","journal-title":"J. Exp. Med."},{"key":"2026012808080675000_r28","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1128\/JVI.74.11.4999-5005.2000","article-title":"Induction of CD4(+) T-cell-independent immunoglobulin responses by inactivated influenza virus.","volume":"74","author":"Sha","year":"2000","journal-title":"J. Virol."},{"key":"2026012808080675000_r29","doi-asserted-by":"crossref","first-page":"5827","DOI":"10.4049\/jimmunol.175.9.5827","article-title":"CD4 T cell-independent antibody response promotes resolution of primary influenza infection and helps to prevent reinfection.","volume":"175","author":"Lee","year":"2005","journal-title":"J. Immunol."},{"key":"2026012808080675000_r30","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S1074-7613(01)00126-1","article-title":"Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo.","volume":"14","author":"Le Bon","year":"2001","journal-title":"Immunity"},{"key":"2026012808080675000_r31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S1074-7613(03)00208-5","article-title":"Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6.","volume":"19","author":"Jego","year":"2003","journal-title":"Immunity"},{"key":"2026012808080675000_r32","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nature02263","article-title":"Protein degradation and protection against misfolded or damaged proteins.","volume":"426","author":"Goldberg","year":"2003","journal-title":"Nature"},{"key":"2026012808080675000_r33","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1016\/j.febslet.2007.04.031","article-title":"Managing and exploiting stress in the antibody factory.","volume":"581","author":"Cenci","year":"2007","journal-title":"FEBS Lett."},{"key":"2026012808080675000_r34","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/eji.200737743","article-title":"Dampening Ab responses using proteasome inhibitors following in vivo B cell activation.","volume":"38","author":"Cascio","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2026012808080675000_r35","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/354395a0","article-title":"Generation of p50 subunit of NF-kappa B by processing of p105 through an ATP-dependent pathway.","volume":"354","author":"Fan","year":"1991","journal-title":"Nature"},{"key":"2026012808080675000_r36","doi-asserted-by":"crossref","first-page":"8646","DOI":"10.1128\/MCB.19.12.8646","article-title":"NOD mice are defective in proteasome production and activation of NF-kappaB.","volume":"19","author":"Hayashi","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"2026012808080675000_r37","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/80349","article-title":"LMP2 expression and proteasome activity in NOD mice.","volume":"6","author":"Runnels","year":"2000","journal-title":"Nat. Med."},{"key":"2026012808080675000_r38","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1096\/fj.08-105940","article-title":"Ischemic preconditioning-induced cardioprotection is lost in mice with immunoproteasome subunit low molecular mass polypeptide-2 deficiency.","volume":"22","author":"Cai","year":"2008","journal-title":"FASEB J."},{"key":"2026012808080675000_r39","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1089\/ars.2006.8.130","article-title":"LMP2 knock-out mice have reduced proteasome activities and increased levels of oxidatively damaged proteins.","volume":"8","author":"Ding","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"2026012808080675000_r40","doi-asserted-by":"crossref","first-page":"11560","DOI":"10.1073\/pnas.0404101101","article-title":"Inhibition of apoptosis in acute promyelocytic leukemia cells leads to increases in levels of oxidized protein and LMP2 immunoproteasome.","volume":"101","author":"Khan","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026012808080675000_r41","doi-asserted-by":"crossref","first-page":"11653","DOI":"10.1523\/JNEUROSCI.23-37-11653.2003","article-title":"Neuronal induction of the immunoproteasome in Huntington\u2019s disease.","volume":"23","author":"D\u00edaz-Hern\u00e1ndez","year":"2003","journal-title":"J. Neurosci."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/8\/4115\/8013310","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/8\/4115\/8013310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:08:31Z","timestamp":1769605711000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/8\/4115\/8013310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":41,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2010,4,15]]},"published-print":{"date-parts":[[2010,4,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0903003","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,4]]},"published":{"date-parts":[[2010,4]]}}}