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Calreticulin was postulated as a chaperone and integral part of the peptide\u2010loading complex of MHC\u2010I. Oncogenic mutations of calreticulin allow surface expression in complex with the thrombopoietin receptor, leading to ligand\u2010independent activation, cell proliferation, and myeloproliferative neoplasms. We hypothesized that mutated calreticulin could also corrupt the function of MHC\u2010I, as previous reports revealed decreased surface expression, peptide\u2010loading defects and retention of MHC\u2010I in the Golgi apparatus. We employed reporter cell models that utilized the T cell response towards target murine and human primary cells and cell lines carrying calreticulin mutations as a functional readout. We also harnessed T cell responses upon a viral infection In\u00a0Vivo. We found no evidence for immunosuppression in mutant calreticulin\u2010expressing or calreticulin\u2010deficient cells. Our study implies an overestimation of the significance of calreticulin for MHC\u2010I functionality and provides an impulse for reevaluation. Furthermore, we show that calreticulin deficiency affects only a few proteins, including myeloperoxidase and other proteins involved in antibacterial immune mechanisms. In conclusion, mutant calreticulins do not interfere with antigen presentation in MPN, making MHC\u2010I\u2010dependent immunotherapies a viable venue for treatment.<\/jats:p>","DOI":"10.1111\/jcmm.71399","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:30:51Z","timestamp":1791775851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Haematopoietic Cells Deficient for Calreticulin or Expressing Its Oncogenic Variants Maintain Functional Antigen Presentation"],"prefix":"10.1111","volume":"30","author":[{"given":"Maria","family":"H\u00f6hrhan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Antonio\u2010Herrera","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM)  Vienna Austria"},{"name":"Institute for Hygiene and Applied Immunology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2026-0163","authenticated-orcid":false,"given":"Henrique G.","family":"Cola\u00e7o","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM)  Vienna Austria"},{"name":"Institute for Hygiene and Applied Immunology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Wagner","sequence":"additional","affiliation":[{"name":"Core Facility Proteomics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Unterwurzacher","sequence":"additional","affiliation":[{"name":"Core Facility Proteomics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2346-5496","authenticated-orcid":false,"given":"Cecilia","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0803-614X","authenticated-orcid":false,"given":"Klaus","family":"Kratochwill","sequence":"additional","affiliation":[{"name":"Core Facility Proteomics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Bergthaler","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM)  Vienna Austria"},{"name":"Institute for Hygiene and Applied Immunology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-8539","authenticated-orcid":false,"given":"Robert","family":"Kralovics","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005\u20102736(89)90166\u20101"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(19)43026\u20103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24627"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.275.17.13089"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032384\u2010z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.179.9.5717"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074\u20107613(00)80487\u20102"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1311347"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1312542"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/BLOOD\u20102015\u201009\u2010671172"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/BLOOD\u20102015\u201011\u2010681932"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201015\u20101434\/42467\/AM\/MUTANT\u2010CALRETICULIN\u2010REQUIRES\u2010BOTH\u2010ITS\u2010MUTANT\u2010C"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","unstructured":"H.Nivarthi D.Chen C.Cleary et\u00a0al. \u201cThrombopoietin Receptor Is Required for the Oncogenic Function of CALR Mutants. 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