{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:08:42Z","timestamp":1774123722118,"version":"3.50.1"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T00:00:00Z","timestamp":1157068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic beryllium disease is a lung disorder caused by beryllium exposure in the workplace and is characterized by granulomatous inflammation and the accumulation of beryllium-specific, HLA-DP2-restricted CD4+ T lymphocytes in the lung that proliferate and secrete Th1-type cytokines. To characterize the interaction among HLA-DP2, beryllium, and CD4+ T cells, we constructed rHLA-DP2 and rHLA-DP4 molecules consisting of the \u03b1-1 and \u03b2-1 domains of the HLA-DP molecules genetically linked into single polypeptide chains. Peptide binding to rHLA-DP2 and rHLA-DP4 was consistent with previously published peptide-binding motifs for these MHC class II molecules, with peptide binding dominated by aromatic residues in the P1 pocket. 9Be nuclear magnetic resonance spectroscopy showed that beryllium binds to the HLA-DP2-derived molecule, with no binding to the HLA-DP4 molecule that differs from DP2 by four amino acid residues. Using beryllium-specific CD4+ T cell lines derived from the lungs of chronic beryllium disease patients, beryllium presentation to those cells was independent of Ag processing because fixed APCs were capable of presenting BeSO4 and inducing T cell proliferation. Exposure of beryllium-specific CD4+ T cells to BeSO4-pulsed, plate-bound rHLA-DP2 molecules induced IFN-\u03b3 secretion. In addition, pretreatment of beryllium-specific CD4+ T cells with BeSO4-pulsed, plate-bound HLA-DP2 blocked proliferation and IL-2 secretion upon re-exposure to beryllium presented by APCs. Thus, the rHLA-DP2 molecules described herein provide a template for engineering variants that retain the ability to tolerize pathogenic CD4+ T cells, but do so in the absence of the beryllium Ag.<\/jats:p>","DOI":"10.4049\/jimmunol.177.6.3874","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:50Z","timestamp":1397848670000},"page":"3874-3883","source":"Crossref","is-referenced-by-count":36,"title":["Recombinant HLA-DP2 Binds Beryllium and Tolerizes Beryllium-Specific Pathogenic CD4+ T Cells"],"prefix":"10.1093","volume":"177","author":[{"given":"Andrew P","family":"Fontenot","sequence":"first","affiliation":[{"name":"Departments of Medicine and Immunology, University of Colorado Health Sciences Center , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy S","family":"Keizer","sequence":"additional","affiliation":[{"name":"Chemistry Division, Los Alamos National Laboratory , Los Alamos, NM 87545"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"McCleskey","sequence":"additional","affiliation":[{"name":"Chemistry Division, Los Alamos National Laboratory , Los Alamos, NM 87545"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas G","family":"Mack","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Immunology, University of Colorado Health Sciences Center , Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Meza-Romero","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianya","family":"Huan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan K","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur A","family":"Vandenbark","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Scott","sequence":"additional","affiliation":[{"name":"Chemistry Division, Los Alamos National Laboratory , Los Alamos, NM 87545"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory G","family":"Burrows","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University , Portland, OR 97239"},{"name":"Department of Biochemistry and Molecular Biology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,9,15]]},"reference":[{"key":"2026020213061326500_R1","first-page":"567","volume-title":"J. 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