{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T09:06:17Z","timestamp":1754557577493},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T00:00:00Z","timestamp":1519084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL 092977"],"award-info":[{"award-number":["R01 HL 092977"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Kell is a glycoprotein expressed on red blood cells (RBCs). Its K and k variants contain either Met (K antigen) or Thr (k antigen) at Position 193, respectively. Development of anti\u2010K after K\u2010mismatched antigen exposure via blood transfusions or pregnancy can destroy RBCs, leading to hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. The immunogenicity of overlapping 15\u2010mer Kell peptides with M193 or T193 at every possible position was investigated previously. Interestingly, Peptide W179 to M193, with the polymorphic M193T residue at the peptide's C\u2010terminus, was the most effective at stimulating CD4 T cells from a series of K\u2010immunized women.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>This study investigates the basis for HLA restriction of anti\u2010K immune responses. Major histocompatibility complex Class II (MHCII)\u2010binding prediction algorithms and quantitative peptide\u2013MHCII\u2010binding assays were employed to determine the binding registers; anchor residues; and affinities of wild\u2010type, truncated, and sequence\u2010modified K and k peptides. Predictions were generated using Immune Epitope Database and ProPred algorithms. Competitive peptide\u2013MHCII\u2010binding assays utilized 12 recombinant HLA\u2010DR proteins, K and k peptides, and high\u2010affinity MHCII\u2010restricted reference peptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The peptide\u2013MHCII\u2010binding assays identified a unique K peptide\u2013binding register (W179\u2010S187) restricted to HLA\u2010DRB1*11:01, in addition to partially overlapping binding registers that included the K\/k M193T polymorphic site and that bound promiscuously to multiple HLA\u2010DR proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Three partially overlapping MHCII\u2010binding motifs for HLA\u2010DRB1*11:01 result in high\u2010avidity K\u2010peptide binding, which may contribute to HLA\u2010DR11\u2010restricted immunogenicity associated with the K allele.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.14525","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T18:49:37Z","timestamp":1519411777000},"page":"1171-1181","source":"Crossref","is-referenced-by-count":1,"title":["A unique major histocompatibility complex Class II\u2013binding register correlates with HLA\u2010DR11\u2013associated immunogenicity of the major K blood group antigen"],"prefix":"10.1111","volume":"58","author":[{"given":"Devi","family":"Gunasekera","sequence":"first","affiliation":[{"name":"Department of Medicine Uniformed Services University of the Health Sciences Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Zimring","sequence":"additional","affiliation":[{"name":"Research Division Bloodworks NW Seattle Washington."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen P.","family":"Pratt","sequence":"additional","affiliation":[{"name":"Department of 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