{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:59:51Z","timestamp":1790837991963,"version":"4.1.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"19","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000781","name":"EC | European Research Council","doi-asserted-by":"publisher","award":["789121"],"award-info":[{"award-number":["789121"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"EC | European Research Council","doi-asserted-by":"publisher","award":["101141396"],"award-info":[{"award-number":["101141396"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TA157\/12-1"],"award-info":[{"award-number":["TA157\/12-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC1507\/P18"],"award-info":[{"award-number":["CRC1507\/P18"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["557111829"],"award-info":[{"award-number":["557111829"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC1507\/P13"],"award-info":[{"award-number":["CRC1507\/P13"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Protein folding in the endoplasmic reticulum (ER) relies on N-linked glycosylation and glycan remodeling to guide quality control. Major histocompatibility complex class I (MHC-I) molecules, essential for adaptive immunity, undergo a specialized maturation pathway involving the peptide-loading complex (PLC), the editor TAPBPR, the UDP-glucose:glycoprotein glucosyltransferase, and the lectin chaperone calreticulin. However, how glycan-dependent mechanisms coordinate MHC-I transfer between these factors has remained unclear. Using a fully reconstituted system, we show that retrograde transfer of peptide-receptive MHC-I from TAPBPR to tapasin requires calreticulin recognition of monoglucosylated MHC-I glycans. While calreticulin\u2019s C-terminal acidic helix is dispensable for releasing reglucosylated MHC-I from TAPBPR, it is essential for productive docking of MHC-I onto tapasin. These findings reveal a glycan-surveillance mechanism that enables retrieval of suboptimally loaded MHC-I molecules missed by the initial quality control at the PLC. Our work defines a glycan-dependent chaperone network, finely tuned by a combination of low-micromolar interactions between the constituents, that ensures efficient MHC-I maturation and illustrates fundamental principles of ER protein quality control.<\/jats:p>","DOI":"10.1038\/s44318-026-00873-2","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:03:39Z","timestamp":1786957419000},"page":"6699-6722","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reconstitution of glycan-driven MHC-I recycling reveals calreticulin as mediator between TAPBPR and tapasin"],"prefix":"10.1038","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0226-3923","authenticated-orcid":false,"given":"Tim J","family":"Heinke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7529-9592","authenticated-orcid":false,"given":"Amin","family":"Fahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niko","family":"Popovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Rath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines K","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-490X","authenticated-orcid":false,"given":"Nina","family":"Morgner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-766X","authenticated-orcid":false,"given":"Simon","family":"Trowitzsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0403-2160","authenticated-orcid":false,"given":"Robert","family":"Tamp\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"873_CR1","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1093\/bioinformatics\/btv639","volume":"32","author":"M Andreatta","year":"2016","unstructured":"Andreatta M, Nielsen M (2016) Gapped sequence alignment using artificial neural networks: application to the MHC class I system. Bioinformatics 32:511\u2013517","journal-title":"Bioinformatics"},{"key":"873_CR2","doi-asserted-by":"publisher","first-page":"9555","DOI":"10.1074\/jbc.RA118.002836","volume":"293","author":"N Arshad","year":"2018","unstructured":"Arshad N, Cresswell P (2018) Tumor-associated calreticulin variants functionally compromise the peptide loading complex and impair its recruitment of MHC-I. J Biol Chem 293:9555\u20139569","journal-title":"J Biol Chem"},{"key":"873_CR3","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/978-3-030-67696-4_8","volume":"59","author":"N Arshad","year":"2021","unstructured":"Arshad N, Cresswell P (2021) Impact of calreticulin and Its mutants on endoplasmic reticulum function in health and disease. Prog Mol Subcell Biol 59:163\u2013180","journal-title":"Prog Mol Subcell Biol"},{"key":"873_CR4","doi-asserted-by":"publisher","first-page":"13563","DOI":"10.1074\/jbc.M113.460436","volume":"288","author":"MK Barker","year":"2013","unstructured":"Barker MK, Rose DR (2013) Specificity of processing alpha-glucosidase I is guided by the substrate conformation: crystallographic and in silico studies. J Biol Chem 288:13563\u201313574","journal-title":"J Biol Chem"},{"key":"873_CR5","doi-asserted-by":"publisher","first-page":"28232","DOI":"10.1073\/pnas.2013554117","volume":"117","author":"AA Bashirova","year":"2020","unstructured":"Bashirova AA, Viard M, Naranbhai V, Grifoni A, Garcia-Beltran W, Akdag M, Yuki Y, Gao X, O\u2019HUigin C, Raghavan M et al (2020) HLA tapasin independence: broader peptide repertoire and HIV control. Proc Natl Acad Sci USA 117:28232\u201328238","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR6","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nature24627","volume":"551","author":"A Blees","year":"2017","unstructured":"Blees A, Januliene D, Hofmann T, Koller N, Schmidt C, Trowitzsch S, Moeller A, Tamp\u00e9 R (2017) Structure of the human MHC-I peptide-loading complex. Nature 551:525\u2013528","journal-title":"Nature"},{"key":"873_CR7","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1146\/annurev-immunol-032712-095910","volume":"31","author":"JS Blum","year":"2013","unstructured":"Blum JS, Wearsch PA, Cresswell P (2013) Pathways of antigen processing. Annu Rev Immunol 31:443\u2013473","journal-title":"Annu Rev Immunol"},{"key":"873_CR8","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.1073\/pnas.1222342110","volume":"110","author":"LH Boyle","year":"2013","unstructured":"Boyle LH, Hermann C, Boname JM, Porter KM, Patel PA, Burr ML, Duncan LM, Harbour ME, Rhodes DA, Skjodt K et al (2013) Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway. Proc Natl Acad Sci USA 110:3465\u20133470","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR9","doi-asserted-by":"publisher","first-page":"a013359","DOI":"10.1101\/cshperspect.a013359","volume":"5","author":"J Breitling","year":"2013","unstructured":"Breitling J, Aebi M (2013) N-linked protein glycosylation in the endoplasmic reticulum. Cold Spring Harb Perspect Biol 5:a013359","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"873_CR10","doi-asserted-by":"publisher","first-page":"E4630","DOI":"10.1073\/pnas.1604463113","volume":"113","author":"AT Caputo","year":"2016","unstructured":"Caputo AT, Alonzi DS, Marti L, Reca IB, Kiappes JL, Struwe WB, Cross A, Basu S, Lowe ED, Darlot B et al (2016) Structures of mammalian ER alpha-glucosidase II capture the binding modes of broad-spectrum iminosugar antivirals. Proc Natl Acad Sci USA 113:E4630\u2013E4638","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR11","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.str.2007.01.011","volume":"15","author":"VT Chang","year":"2007","unstructured":"Chang VT, Crispin M, Aricescu AR, Harvey DJ, Nettleship JE, Fennelly JA, Yu C, Boles KS, Evans EJ, Stuart DI et al (2007) Glycoprotein structural genomics: solving the glycosylation problem. Structure 15:267\u2013273","journal-title":"Structure"},{"key":"873_CR12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05345","volume":"4","author":"P Chappell","year":"2015","unstructured":"Chappell P, Meziane el K, Harrison M, Magiera L, Hermann C, Mears L, Wrobel AG, Durant C, Nielsen LL, Buus S et al (2015) Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding. eLife 4:e05345","journal-title":"eLife"},{"key":"873_CR13","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1038\/sj.emboj.7601624","volume":"26","author":"M Chen","year":"2007","unstructured":"Chen M, Bouvier M (2007) Analysis of interactions in a tapasin\/class I complex provides a mechanism for peptide selection. EMBO J 26:1681\u20131690","journal-title":"EMBO J"},{"key":"873_CR14","doi-asserted-by":"publisher","first-page":"4520","DOI":"10.1074\/jbc.M109.085407","volume":"285","author":"N Del Cid","year":"2010","unstructured":"Del Cid N, Jeffery E, Rizvi SM, Stamper E, Peters LR, Brown WC, Provoda C, Raghavan M (2010) Modes of calreticulin recruitment to the major histocompatibility complex class I assembly pathway. J Biol Chem 285:4520\u20134535","journal-title":"J Biol Chem"},{"key":"873_CR15","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.molcel.2005.05.029","volume":"19","author":"P Deprez","year":"2005","unstructured":"Deprez P, Gautschi M, Helenius A (2005) More than one glycan is needed for ER glucosidase II to allow entry of glycoproteins into the calnexin\/calreticulin cycle. Mol Cell 19:183\u2013195","journal-title":"Mol Cell"},{"key":"873_CR16","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/S1074-7613(02)00263-7","volume":"16","author":"TP Dick","year":"2002","unstructured":"Dick TP, Bangia N, Peaper DR, Cresswell P (2002) Disulfide bond isomerization and the assembly of MHC class I-peptide complexes. Immunity 16:87\u201398","journal-title":"Immunity"},{"key":"873_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32384-z","volume":"13","author":"A Domnick","year":"2022","unstructured":"Domnick A, Winter C, Su\u0161ac L, Hennecke L, Hensen M, Zitzmann N, Trowitzsch S, Thomas C, Tamp\u00e9 R (2022) Molecular basis of MHC I quality control in the peptide loading complex. Nat Commun 13:4701","journal-title":"Nat Commun"},{"key":"873_CR18","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.immuni.2008.10.018","volume":"30","author":"G Dong","year":"2009","unstructured":"Dong G, Wearsch PA, Peaper DR, Cresswell P, Reinisch KM (2009) Insights into MHC class I peptide loading from the structure of the tapasin-ERp57 thiol oxidoreductase heterodimer. Immunity 30:21\u201332","journal-title":"Immunity"},{"key":"873_CR19","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1096\/fasebj.5.15.1743438","volume":"5","author":"AD Elbein","year":"1991","unstructured":"Elbein AD (1991) Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing. FASEB J 5:3055\u20133063","journal-title":"FASEB J"},{"key":"873_CR20","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1158\/2159-8290.CD-15-1434","volume":"6","author":"S Elf","year":"2016","unstructured":"Elf S, Abdelfattah NS, Chen E, Perales-Paton J, Rosen EA, Ko A, Peisker F, Florescu N, Giannini S, Wolach O et al (2016) Mutant calreticulin requires both Its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation. Cancer Discov 6:368\u2013381","journal-title":"Cancer Discov"},{"key":"873_CR21","doi-asserted-by":"publisher","first-page":"4503","DOI":"10.4049\/jimmunol.1501515","volume":"195","author":"G Fleischmann","year":"2015","unstructured":"Fleischmann G, Fisette O, Thomas C, Wieneke R, Tumulka F, Schneeweiss C, Springer S, Sch\u00e4fer LV, Tamp\u00e9 R (2015) Mechanistic basis for epitope proofreading in the peptide-loading complex. J Immunol 195:4503\u20134513","journal-title":"J Immunol"},{"key":"873_CR22","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1073\/pnas.042699099","volume":"99","author":"EM Frickel","year":"2002","unstructured":"Frickel EM, Riek R, Jelesarov I, Helenius A, Wuthrich K, Ellgaard L (2002) TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain. Proc Natl Acad Sci USA 99:1954\u20131959","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR23","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S1074-7613(01)00260-6","volume":"16","author":"B Gao","year":"2002","unstructured":"Gao B, Adhikari R, Howarth M, Nakamura K, Gold MC, Hill AB, Knee R, Michalak M, Elliott T (2002) Assembly and antigen-presenting function of MHC class I molecules in cells lacking the ER chaperone calreticulin. Immunity 16:99\u2013109","journal-title":"Immunity"},{"key":"873_CR24","doi-asserted-by":"publisher","first-page":"30680","DOI":"10.1074\/jbc.M701721200","volume":"282","author":"M Garstka","year":"2007","unstructured":"Garstka M, Borchert B, Al-Balushi M, Praveen PV, Kuhl N, Majoul I, Duden R, Springer S (2007) Peptide-receptive major histocompatibility complex class I molecules cycle between endoplasmic reticulum and cis-Golgi in wild-type lymphocytes. J Biol Chem 282:30680\u201330690","journal-title":"J Biol Chem"},{"key":"873_CR25","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41586-022-05638-5","volume":"614","author":"M Gemmer","year":"2023","unstructured":"Gemmer M, Chaillet ML, van Loenhout J, Cuevas Arenas R, Vismpas D, Grollers-Mulderij M, Koh FA, Albanese P, Scheltema RA, Howes SC et al (2023) Visualization of translation and protein biogenesis at the ER membrane. Nature 614:160\u2013167","journal-title":"Nature"},{"key":"873_CR26","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/s41580-025-00855-y","volume":"26","author":"KP Guay","year":"2025","unstructured":"Guay KP, Chou WC, Canniff NP, Paul KB, Hebert DN (2025) N-glycan-dependent protein maturation and quality control in the ER. Nat Rev Mol Cell Biol 26:926\u2013939","journal-title":"Nat Rev Mol Cell Biol"},{"key":"873_CR27","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1126\/science.291.5512.2364","volume":"291","author":"A Helenius","year":"2001","unstructured":"Helenius A, Aebi M (2001) Intracellular functions of N-linked glycans. Science 291:2364\u20132369","journal-title":"Science"},{"key":"873_CR28","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1146\/annurev.biochem.73.011303.073752","volume":"73","author":"A Helenius","year":"2004","unstructured":"Helenius A, Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73:1019\u20131049","journal-title":"Annu Rev Biochem"},{"key":"873_CR29","doi-asserted-by":"publisher","first-page":"5743","DOI":"10.4049\/jimmunol.1300929","volume":"191","author":"C Hermann","year":"2013","unstructured":"Hermann C, Strittmatter LM, Deane JE, Boyle LH (2013) The binding of TAPBPR and Tapasin to MHC class I is mutually exclusive. J Immunol 191:5743\u20135750","journal-title":"J Immunol"},{"key":"873_CR30","doi-asserted-by":"publisher","unstructured":"Hermann C, van Hateren A, Trautwein N, Neerincx A, Duriez PJ, Stevanovic S, Trowsdale J, Deane JE, Elliott T, Boyle LH (2015) TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst. eLife https:\/\/doi.org\/10.7554\/eLife.09617","DOI":"10.7554\/eLife.09617"},{"key":"873_CR31","doi-asserted-by":"publisher","first-page":"11737","DOI":"10.1073\/pnas.0306294101","volume":"101","author":"M Howarth","year":"2004","unstructured":"Howarth M, Williams A, Tolstrup AB, Elliott T (2004) Tapasin enhances MHC class I peptide presentation according to peptide half-life. Proc Natl Acad Sci USA 101:11737\u201311742","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR32","doi-asserted-by":"publisher","first-page":"3730","DOI":"10.1038\/emboj.2009.296","volume":"28","author":"C Howe","year":"2009","unstructured":"Howe C, Garstka M, Al-Balushi M, Ghanem E, Antoniou AN, Fritzsche S, Jankevicius G, Kontouli N, Schneeweiss C, Williams A et al (2009) Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class I molecules. EMBO J 28:3730\u20133744","journal-title":"EMBO J"},{"key":"873_CR33","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/j.celrep.2019.09.074","volume":"29","author":"FT Ilca","year":"2019","unstructured":"Ilca FT, Drexhage LZ, Brewin G, Peacock S, Boyle LH (2019) Distinct polymorphisms in HLA class I molecules govern their susceptibility to peptide editing by TAPBPR. Cell Rep 29:1621\u20131632.e1623","journal-title":"Cell Rep"},{"key":"873_CR34","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1126\/science.aao5154","volume":"358","author":"J Jiang","year":"2017","unstructured":"Jiang J, Natarajan K, Boyd LF, Morozov GI, Mage MG, Margulies DH (2017) Crystal structure of a TAPBPR-MHC I complex reveals the mechanism of peptide editing in antigen presentation. Science 358:1064\u20131068","journal-title":"Science"},{"key":"873_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33153-8","volume":"13","author":"J Jiang","year":"2022","unstructured":"Jiang J, Taylor DK, Kim EJ, Boyd LF, Ahmad J, Mage MG, Truong HV, Woodward CH, Sgourakis NG, Cresswell P et al (2022) Structural mechanism of tapasin-mediated MHC-I peptide loading in antigen presentation. Nat Commun 13:5470","journal-title":"Nat Commun"},{"key":"873_CR36","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1021\/bi0355286","volume":"43","author":"M Kapoor","year":"2004","unstructured":"Kapoor M, Ellgaard L, Gopalakrishnapai J, Schirra C, Gemma E, Oscarson S, Helenius A, Surolia A (2004) Mutational analysis provides molecular insight into the carbohydrate-binding region of calreticulin: pivotal roles of tyrosine-109 and aspartate-135 in carbohydrate recognition. Biochemistry 43:97\u2013106","journal-title":"Biochemistry"},{"key":"873_CR37","doi-asserted-by":"publisher","first-page":"6194","DOI":"10.1074\/jbc.M209132200","volume":"278","author":"M Kapoor","year":"2003","unstructured":"Kapoor M, Srinivas H, Kandiah E, Gemma E, Ellgaard L, Oscarson S, Helenius A, Surolia A (2003) Interactions of substrate with calreticulin, an endoplasmic reticulum chaperone. J Biol Chem 278:6194\u20136200","journal-title":"J Biol Chem"},{"key":"873_CR38","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1056\/NEJMoa1311347","volume":"369","author":"T Klampfl","year":"2013","unstructured":"Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D et al (2013) Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369:2379\u20132390","journal-title":"N Engl J Med"},{"key":"873_CR39","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.1111\/febs.15330","volume":"287","author":"G Kozlov","year":"2020","unstructured":"Kozlov G, Gehring K (2020) Calnexin cycle - structural features of the ER chaperone system. FEBS J 287:4322\u20134340. https:\/\/doi.org\/10.1111\/febs.15330","journal-title":"FEBS J"},{"key":"873_CR40","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/j.str.2006.06.019","volume":"14","author":"G Kozlov","year":"2006","unstructured":"Kozlov G, Maattanen P, Schrag JD, Pollock S, Cygler M, Nagar B, Thomas DY, Gehring K (2006) Crystal structure of the bb\u2019 domains of the protein disulfide isomerase ERp57. Structure 14:1331\u20131339","journal-title":"Structure"},{"key":"873_CR41","doi-asserted-by":"publisher","first-page":"38612","DOI":"10.1074\/jbc.M110.168294","volume":"285","author":"G Kozlov","year":"2010","unstructured":"Kozlov G, Pocanschi CL, Rosenauer A, Bastos-Aristizabal S, Gorelik A, Williams DB, Gehring K (2010) Structural basis of carbohydrate recognition by calreticulin. J Biol Chem 285:38612\u201338620","journal-title":"J Biol Chem"},{"key":"873_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.102987","volume":"299","author":"BH Lan","year":"2023","unstructured":"Lan BH, Becker M, Freund C (2023) The mode of action of tapasin on major histocompatibility class I (MHC-I) molecules. J Biol Chem 299:102987","journal-title":"J Biol Chem"},{"key":"873_CR43","doi-asserted-by":"publisher","first-page":"E1006","DOI":"10.1073\/pnas.1519894113","volume":"113","author":"GI Morozov","year":"2016","unstructured":"Morozov GI, Zhao H, Mage MG, Boyd LF, Jiang J, Dolan MA, Venna R, Norcross MA, McMurtrey CP, Hildebrand W et al (2016) Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing. Proc Natl Acad Sci USA 113:E1006\u2013E1015","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32841-9","volume":"13","author":"IK M\u00fcller","year":"2022","unstructured":"M\u00fcller IK, Winter C, Thomas C, Spaapen RM, Trowitzsch S, Tamp\u00e9 R (2022) Structure of an MHC I-tapasin-ERp57 editing complex defines chaperone promiscuity. Nat Commun 13:5383","journal-title":"Nat Commun"},{"key":"873_CR45","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1056\/NEJMoa1312542","volume":"369","author":"J Nangalia","year":"2013","unstructured":"Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG et al (2013) Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 369:2391\u20132405","journal-title":"N Engl J Med"},{"key":"873_CR46","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.molimm.2018.06.269","volume":"113","author":"A Neerincx","year":"2019","unstructured":"Neerincx A, Boyle LH (2019) Preferential interaction of MHC class I with TAPBPR in the absence of glycosylation. Mol Immunol 113:58\u201366","journal-title":"Mol Immunol"},{"key":"873_CR47","doi-asserted-by":"publisher","unstructured":"Neerincx A, Hermann C, Antrobus R, van Hateren A, Cao H, Trautwein N, Stevanovic S, Elliott T, Deane JE, Boyle LH (2017) TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway. eLife https:\/\/doi.org\/10.7554\/eLife.23049","DOI":"10.7554\/eLife.23049"},{"key":"873_CR48","doi-asserted-by":"publisher","unstructured":"Ninagawa S, Matsuo M, Ying D, Oshita S, Aso S, Matsushita K, Taniguchi M, Fueki A, Yamashiro M, Sugasawa K et al (2024) UGGT1-mediated reglucosylation of N-glycan competes with ER-associated degradation of unstable and misfolded glycoproteins. eLife https:\/\/doi.org\/10.7554\/eLife.93117.2","DOI":"10.7554\/eLife.93117.2"},{"key":"873_CR49","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1093\/protein\/gzaa015","volume":"32","author":"SM O\u2019Rourke","year":"2019","unstructured":"O\u2019Rourke SM, Morozov GI, Roberts JT, Barb AW, Sgourakis NG (2019) Production of soluble pMHC-I molecules in mammalian cells using the molecular chaperone TAPBPR. Protein Eng Des Sel 32:525\u2013532","journal-title":"Protein Eng Des Sel"},{"key":"873_CR50","doi-asserted-by":"publisher","first-page":"8260","DOI":"10.1016\/S0021-9258(20)82057-2","volume":"258","author":"AJ Parodi","year":"1983","unstructured":"Parodi AJ, Mendelzon DH, Lederkremer GZ (1983) Transient glucosylation of protein-bound Man9GlcNAc2, Man8GlcNAc2, and Man7GlcNAc2 in calf thyroid cells. A possible recognition signal in the processing of glycoproteins. J Biol Chem 258:8260\u20138265","journal-title":"J Biol Chem"},{"key":"873_CR51","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41577-022-00707-2","volume":"22","author":"N Pishesha","year":"2022","unstructured":"Pishesha N, Harmand TJ, Ploegh HL (2022) A guide to antigen processing and presentation. Nat Rev Immunol 22:751\u2013764","journal-title":"Nat Rev Immunol"},{"key":"873_CR52","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.4049\/jimmunol.166.2.1016","volume":"166","author":"AW Purcell","year":"2001","unstructured":"Purcell AW, Gorman JJ, Garcia-Peydro M, Paradela A, Burrows SR, Talbo GH, Laham N, Peh CA, Reynolds EC, Lopez De Castro JA et al (2001) Quantitative and qualitative influences of tapasin on the class I peptide repertoire. J Immunol 166:1016\u20131027","journal-title":"J Immunol"},{"key":"873_CR53","doi-asserted-by":"publisher","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","volume":"48","author":"B Reynisson","year":"2020","unstructured":"Reynisson B, Alvarez B, Paul S, Peters B, Nielsen M (2020) NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res 48:W449\u2013W454","journal-title":"Nucleic Acids Res"},{"key":"873_CR54","doi-asserted-by":"publisher","first-page":"4967","DOI":"10.4049\/jimmunol.1301670","volume":"192","author":"SM Rizvi","year":"2014","unstructured":"Rizvi SM, Salam N, Geng J, Qi Y, Bream JH, Duggal P, Hussain SK, Martinson J, Wolinsky SM, Carrington M et al (2014) Distinct assembly profiles of HLA-B molecules. J Immunol 192:4967\u20134976","journal-title":"J Immunol"},{"key":"873_CR55","doi-asserted-by":"publisher","first-page":"8544","DOI":"10.1073\/pnas.1703682114","volume":"114","author":"P Roversi","year":"2017","unstructured":"Roversi P, Marti L, Caputo AT, Alonzi DS, Hill JC, Dent KC, Kumar A, Levasseur MD, Lia A, Waksman T et al (2017) Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. Proc Natl Acad Sci USA 114:8544\u20138549","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR56","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/S1074-7613(00)80487-2","volume":"5","author":"B Sadasivan","year":"1996","unstructured":"Sadasivan B, Lehner PJ, Ortmann B, Spies T, Cresswell P (1996) Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP. Immunity 5:103\u2013114","journal-title":"Immunity"},{"key":"873_CR57","doi-asserted-by":"publisher","unstructured":"Sagert L, Hennig F, Thomas C, Tamp\u00e9 R (2020) A loop structure allows TAPBPR to exert its dual function as MHC I chaperone and peptide editor. eLife https:\/\/doi.org\/10.7554\/eLife.55326","DOI":"10.7554\/eLife.55326"},{"key":"873_CR58","doi-asserted-by":"publisher","unstructured":"Sagert L, Winter C, Ruppert I, Zehetmaier M, Thomas C, Tamp\u00e9 R (2023) The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. eLife https:\/\/doi.org\/10.7554\/eLife.85432","DOI":"10.7554\/eLife.85432"},{"key":"873_CR59","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671\u2013675","journal-title":"Nat Methods"},{"key":"873_CR60","doi-asserted-by":"publisher","first-page":"4196","DOI":"10.1002\/j.1460-2075.1995.tb00093.x","volume":"14","author":"M Sousa","year":"1995","unstructured":"Sousa M, Parodi AJ (1995) The molecular basis for the recognition of misfolded glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. EMBO J 14:4196\u20134203","journal-title":"EMBO J"},{"key":"873_CR61","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1021\/bi00116a015","volume":"31","author":"MC Sousa","year":"1992","unstructured":"Sousa MC, Ferrero-Garcia MA, Parodi AJ (1992) Recognition of the oligosaccharide and protein moieties of glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. Biochemistry 31:97\u2013105","journal-title":"Biochemistry"},{"key":"873_CR62","doi-asserted-by":"crossref","unstructured":"Stolz M, Su\u0161ac L, Fahim A, Keller R, Mancia F, Trowitzsch S, Tamp\u00e9 R (2026) Architectural principles of transporter-chaperone coupling within the native MHC I peptide-loading complex. Sci Adv 12:eaea7735","DOI":"10.1126\/sciadv.aea7735"},{"key":"873_CR63","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade7151","volume":"9","author":"Y Sun","year":"2023","unstructured":"Sun Y, Papadaki GF, Devlin CA, Danon JN, Young MC, Winters TJ, Burslem GM, Procko E, Sgourakis NG (2023) Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes. Sci Adv 9:eade7151","journal-title":"Sci Adv"},{"key":"873_CR64","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.4049\/jimmunol.168.4.1950","volume":"168","author":"P Tan","year":"2002","unstructured":"Tan P, Kropshofer H, Mandelboim O, Bulbuc N, Hammerling GJ, Momburg F (2002) Recruitment of MHC class I molecules by tapasin into the transporter associated with antigen processing-associated complex is essential for optimal peptide loading. J Immunol 168:1950\u20131960","journal-title":"J Immunol"},{"key":"873_CR65","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1126\/science.aao6001","volume":"358","author":"C Thomas","year":"2017","unstructured":"Thomas C, Tamp\u00e9 R (2017) Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing. Science 358:1060\u20131064","journal-title":"Science"},{"key":"873_CR66","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jsb.2010.02.010","volume":"172","author":"S Trowitzsch","year":"2010","unstructured":"Trowitzsch S, Bieniossek C, Nie Y, Garzoni F, Berger I (2010) New baculovirus expression tools for recombinant protein complex production. J Struct Biol 172:45\u201354","journal-title":"J Struct Biol"},{"key":"873_CR67","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1146\/annurev-biophys-121219-081643","volume":"49","author":"S Trowitzsch","year":"2020","unstructured":"Trowitzsch S, Tamp\u00e9 R (2020) Multifunctional chaperone and quality control complexes in adaptive immunity. Annu Rev Biophys 49:135\u2013161","journal-title":"Annu Rev Biophys"},{"key":"873_CR68","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/ni1485","volume":"8","author":"PA Wearsch","year":"2007","unstructured":"Wearsch PA, Cresswell P (2007) Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer. Nat Immunol 8:873\u2013881","journal-title":"Nat Immunol"},{"key":"873_CR69","doi-asserted-by":"publisher","first-page":"25112","DOI":"10.1074\/jbc.M401721200","volume":"279","author":"PA Wearsch","year":"2004","unstructured":"Wearsch PA, Jakob CA, Vallin A, Dwek RA, Rudd PM, Cresswell P (2004) Major histocompatibility complex class I molecules expressed with monoglucosylated N-linked glycans bind calreticulin independently of their assembly status. J Biol Chem 279:25112\u201325121","journal-title":"J Biol Chem"},{"key":"873_CR70","doi-asserted-by":"publisher","first-page":"4950","DOI":"10.1073\/pnas.1102524108","volume":"108","author":"PA Wearsch","year":"2011","unstructured":"Wearsch PA, Peaper DR, Cresswell P (2011) Essential glycan-dependent interactions optimize MHC class I peptide loading. Proc Natl Acad Sci USA 108:4950\u20134955","journal-title":"Proc Natl Acad Sci USA"},{"key":"873_CR71","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/S1074-7613(02)00304-7","volume":"16","author":"AP Williams","year":"2002","unstructured":"Williams AP, Peh CA, Purcell AW, McCluskey J, Elliott T (2002) Optimization of the MHC class I peptide cargo is dependent on tapasin. Immunity 16:509\u2013520","journal-title":"Immunity"},{"key":"873_CR72","doi-asserted-by":"publisher","first-page":"4956","DOI":"10.1073\/pnas.1102527108","volume":"108","author":"W Zhang","year":"2011","unstructured":"Zhang W, Wearsch PA, Zhu Y, Leonhardt RM, Cresswell P (2011) A role for UDP-glucose glycoprotein glucosyltransferase in expression and quality control of MHC class I molecules. Proc Natl Acad Sci USA 108:4956\u20134961","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44318-026-00873-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/s44318-026-00873-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44318-026-00873-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:34:14Z","timestamp":1790836454000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/s44318-026-00873-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":72,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10,1]]}},"alternative-id":["873"],"URL":"https:\/\/doi.org\/10.1038\/s44318-026-00873-2","relation":{},"ISSN":["1460-2075"],"issn-type":[{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"23 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}]}}