{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:50:17Z","timestamp":1788889817376,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T00:00:00Z","timestamp":1542844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1P50AI074321\u201001"],"award-info":[{"award-number":["1P50AI074321\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Genetic variation at <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DRB<\/jats:styled-content>1 is a risk factor for visceral leishmaniasis (<jats:styled-content style=\"fixed-case\">VL<\/jats:styled-content>) caused by <jats:italic>Leishmania donovani<\/jats:italic>. The single nucleotide polymorphism <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"DDBJ\/EMBL\/GenBank\" xlink:href=\"rs9271252\">rs9271252<\/jats:ext-link> upstream of the <jats:italic><jats:styled-content style=\"fixed-case\">DRB<\/jats:styled-content>1<\/jats:italic> gene provides a perfect tag for protective versus risk <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DRB<\/jats:styled-content>1 four\u2010digit alleles. In addition to the traditional role of the membrane\u2010distal region of <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> molecules in antigen presentation and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 T\u2010cell activation, the membrane\u2010proximal region mediates \u2018non\u2010traditional\u2019 multi\u2010functional activation, differentiation, or death signals, including in <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\u2010expressing T cells. To understand how <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> contributes to disease pathogenesis, we examined expression at the protein level in circulating myeloid (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14<jats:sup>+<\/jats:sup>, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>+<\/jats:sup>) and lymphoid (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup>, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19<jats:sup>+<\/jats:sup>) cells of <jats:styled-content style=\"fixed-case\">VL<\/jats:styled-content> patients (pre\u2010 and post\u2010treatment) compared with endemic healthy controls (<jats:styled-content style=\"fixed-case\">EHC<\/jats:styled-content>). Although <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> expression is reduced in circulating myeloid cells in active disease relative to <jats:styled-content style=\"fixed-case\">EHC<\/jats:styled-content> and post\u2010treatment groups, expression is enhanced on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content><jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content><jats:sup>+<\/jats:sup> T cells consistent with T\u2010cell activation. Cells of all myeloid and lymphoid populations from active cases were refractory to stimulation of <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> expression with interferon\u2010<jats:italic>\u03b3<\/jats:italic> (IFN\u2010<jats:italic>\u03b3<\/jats:italic>). In contrast, all populations except <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19<jats:sup>+<\/jats:sup> B cells from healthy blood bank controls showed enhanced <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> expression following IFN\u2010<jats:italic>\u03b3<\/jats:italic> stimulation. The <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"DDBJ\/EMBL\/GenBank\" xlink:href=\"rs9271252\">rs9271252<\/jats:ext-link> genotype did not impact significantly on IFN\u2010<jats:italic>\u03b3<\/jats:italic>\u2010activated <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> expression in myeloid, B or <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells, but <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells from healthy individuals homozygous for the risk allele were particularly refractory to activated <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> expression. Further analysis of <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> expression on subsets of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells regulating <jats:styled-content style=\"fixed-case\">VL<\/jats:styled-content> disease could uncover additional ways in which pleiotropy at <jats:styled-content style=\"fixed-case\">HLA <\/jats:styled-content><jats:italic><jats:styled-content style=\"fixed-case\">DRB<\/jats:styled-content>1<\/jats:italic> contributes to disease pathogenesis.<\/jats:p>","DOI":"10.1111\/imm.13018","type":"journal-article","created":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T14:18:36Z","timestamp":1541600316000},"page":"174-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>HLA<\/scp>\u2010<scp>DR<\/scp> Class <scp>II<\/scp> expression on myeloid and lymphoid cells in relation to 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