{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:48:35Z","timestamp":1791251315556,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,13]]},"abstract":"<jats:p>\n                    Graft loss from chronic rejection has become the major obstacle to the long-term success of whole organ transplantation. In cardiac allografts, chronic rejection is manifested as a diffuse and accelerated form of arteriosclerosis, termed cardiac allograft vasculopathy. It has been suggested that T-cell recognition of processed alloantigens (allopeptides) presented by recipient antigen-presenting cells through the indirect pathway of allorecognition plays a critical role in the development and progression of chronic rejection. However, definitive preclinical evidence to support this hypothesis is lacking. To examine the role of indirect allorecognition in a clinically relevant large animal model of cardiac allograft vasculopathy, we immunized MHC inbred miniature swine with synthetic polymorphic peptides spanning the \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    domain of an allogeneic donor-derived swine leukocyte antigen class I gene. Pigs immunized with swine leukocyte antigen class I allopeptides showed\n                    <jats:italic>in vitro<\/jats:italic>\n                    proliferative responses and\n                    <jats:italic>in vivo<\/jats:italic>\n                    delayed-type hypersensitivity responses to the allogeneic peptides. Donor MHC class I disparate hearts transplanted into peptide-immunized cyclosporine-treated pigs not only rejected faster than unimmunized cyclosporine-treated controls (mean survival time = 5.5 +\/\u22121.7 vs. 54.7 +\/\u22123.8 days,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001), but they also developed obstructive fibroproliferative coronary artery lesions much earlier than unimmunized controls (&lt;9 vs. &gt;30 days). These results definitively link indirect allorecognition and cardiac allograft vasculopathy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.051584498","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"3276-3281","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":109,"title":["Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy"],"prefix":"10.1073","volume":"98","author":[{"given":"Richard S.","family":"Lee","sequence":"first","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Yamada","sequence":"additional","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart L.","family":"Houser","sequence":"additional","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl L.","family":"Womer","sequence":"additional","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaella E.","family":"Maloney","sequence":"additional","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris S.","family":"Rose","sequence":"additional","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H.","family":"Sayegh","sequence":"additional","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joren C.","family":"Madsen","sequence":"additional","affiliation":[{"name":"The Transplantation Biology Research Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114; and Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,3,13]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806183382506"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.6.1643"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(90)90033-6"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199301000-00033"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901143400207"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1117"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.13.1257"},{"key":"e_1_3_3_8_2","first-page":"11","volume":"1","author":"Vella J P","year":"1998","unstructured":"J P Vella, A Knoflach, A M Waaga, M H Sayegh Graft 1 (Suppl. 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