{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T01:17:53Z","timestamp":1769649473132,"version":"3.49.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"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":[[2009,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To present virus and tumor Ags, HLA class I molecules undergo a complex multistep assembly involving discrete but transient folding intermediates. The most extensive folding abnormalities occur in cells lacking the class I L chain subunit, called \u03b22-microglobulin (\u03b22m). Herein, this issue was investigated taking advantage of eight conformational murine mAbs (including the prototypic W6\/32 mAb) to mapped H chain epitopes of class I molecules, four human mAbs to class I alloantigens, as well as radioimmunoprecipitation, in vitro assembly, pulse-chase, flow cytometry, and peptide-pulse\/ELISPOT experiments. We show that endogenous (HLA-A1, -A66, and -B58) as well as transfected (HLA-A2) heavy chains in \u03b22m-defective Burkitt lymphoma Daudi cells are capable of being expressed on the cell surface, although at low levels, and exclusively as immature glycoforms. In addition, HLA-A2 is: 1) partially folded at crucial interfaces with \u03b22m, peptide Ag, and CD8; 2) receptive to exogenous peptide; and 3) capable of presenting exogenous peptide epitopes (from virus and tumor Ags) to cytotoxic T lymphocytes (bulk populations as well as clones) educated in a \u03b22m-positive environment. These experiments demonstrate a precursor-product relationship between novel HLA class I folding intermediates, and define a stepwise mechanism whereby distinct interfaces of the class I H chain undergo successive, ligand-induced folding adjustments in vitro as well as in vivo. Due to this unprecedented class I plasticity, Daudi is the first human cell line in which folding and function of class I HLA molecules are observed in the absence of \u03b22m. These findings bear potential implications for tumor immunotherapy.<\/jats:p>","DOI":"10.4049\/jimmunol.0802316","type":"journal-article","created":{"date-parts":[[2009,3,5]],"date-time":"2009-03-05T20:01:20Z","timestamp":1236283280000},"page":"3609-3617","source":"Crossref","is-referenced-by-count":19,"title":["Class I HLA Folding and Antigen Presentation in \u03b22-Microglobulin-Defective Daudi Cells"],"prefix":"10.1093","volume":"182","author":[{"given":"Aline","family":"Martayan","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, Regina Elena Cancer Institute Centro della Ricerca Sperimentale , Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Sibilio","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Regina Elena Cancer Institute Centro della Ricerca Sperimentale , Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Tremante","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Regina Elena Cancer Institute Centro della Ricerca Sperimentale , Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa Lo","family":"Monaco","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Regina Elena Cancer Institute Centro della Ricerca Sperimentale , Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arend","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doriana","family":"Fruci","sequence":"additional","affiliation":[{"name":"Research Center \u201cOspedale Bambino Ges\u00f9 ,\u201d Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Cova","sequence":"additional","affiliation":[{"name":"Unit of Immunotherapy of Human Tumors, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori , Milan,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Licia","family":"Rivoltini","sequence":"additional","affiliation":[{"name":"Unit of Immunotherapy of Human Tumors, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori , Milan,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizio","family":"Giacomini","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Regina Elena Cancer Institute Centro della Ricerca Sperimentale , Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,3,15]]},"reference":[{"key":"2026012807055624000_R1","first-page":"277","article-title":"Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A\u00b0 resolution.","volume-title":"J. 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