{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:07:04Z","timestamp":1776312424313,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T00:00:00Z","timestamp":1548374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009741","name":"National Blood Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009741","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL114525\u201001A1"],"award-info":[{"award-number":["R01 HL114525\u201001A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Humoral alloimmunization to human leukocyte antigen (HLA) can represent a barrier to solid\u2010organ transplantation, can lead to a refractory state in patients requiring platelet transfusion, and can also contribute to transfusion\u2010related acute lung injury (TRALI). While exposure to HLA\u2010mismatched cells\/tissues are generally required for HLA alloimmunization, the effect of the extent of major histocompatibility complex (MHC) mismatch between donor and recipient is poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>A novel mouse was generated that allows the expression of a single MHC Class I alloantigen, K<jats:sup>d<\/jats:sup>. Alloimmune responses to K<jats:sup>d<\/jats:sup> were studied in C57BL\/6 mice transfused with splenocytes from different donor mice, allowing the analysis of responses to K<jats:sup>d<\/jats:sup> as an isolated alloantigen, or in the context of additional mismatched MHC molecules. Advanced tools were utilized to study responses to K<jats:sup>d<\/jats:sup>, including T\u2010cell receptor transgenic mice that recognize the immunodominant K<jats:sup>d<\/jats:sup> peptide presented by C57BL\/6 mice to CD4+ T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A single MHC Class I alloantigen mismatch is less immunogenic than when the same alloantigen is encountered in the context of additional mismatched MHC alloantigens. This difference is due, at least in part, to induction of CD4+ helper T cells, as the effect is overcome by increasing either mature CD4+ T\u2010cell help through immunization or by increasing the precursor frequency of na\u00efve CD4+ T cells by adoptive transfer from T\u2010cell receptor transgenic donors.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>These findings indicate that the immunogenicity of a single alloantigen can be affected by the context in which it is encountered, demonstrating the potential for cooperative effects between different mismatched MHC alloantigens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.15109","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T16:00:27Z","timestamp":1548432027000},"page":"744-753","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Alloimmunogenicity of an isolated MHC allele is affected by the context of MHC mismatch in a murine model"],"prefix":"10.1111","volume":"59","author":[{"given":"Krystalyn E.","family":"Hudson","sequence":"first","affiliation":[{"name":"BloodworksNW Research Institute  Seattle Washington"},{"name":"Department of Laboratory Medicine University of Washington School of Medicine  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea S.L.","family":"Wong","sequence":"additional","affiliation":[{"name":"BloodworksNW Research Institute  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda L.","family":"Richards","sequence":"additional","affiliation":[{"name":"BloodworksNW Research Institute  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda M.","family":"Kapp","sequence":"additional","affiliation":[{"name":"BloodworksNW Research Institute  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Zimring","sequence":"additional","affiliation":[{"name":"BloodworksNW Research Institute  Seattle Washington"},{"name":"Department of Laboratory Medicine University of Washington School of Medicine  Seattle Washington"},{"name":"Department of Medicine, Division of Hematology University of Washington School of Medicine  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200002150-00001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-493-7_2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180236"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2016.10.002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12687"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13597"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13459"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12048"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318186d87b"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12512"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-6143.2004.00596.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200580"},{"key":"e_1_2_7_14_1","first-page":"805","article-title":"Indirect allorecognition of platelets by T helper cells during platelet transfusions correlates with anti\u2013major histocompatibility complex antibody and cytotoxic T lymphocyte formation","volume":"86","author":"Semple JW","year":"1995","journal-title":"Blood"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000355"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2010.01351.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.2.690"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.007"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062319"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3803"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.4049\/jimmunol.130.2.614","article-title":"Activation of antigen\u2010enriched B cells. 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