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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5103-5110. Prepublished online as a Blood First Edition Paper on September 24, 2008; DOI 10.1182/blood-2008-04-150748. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-04-150748v1 112/13/5103    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tjon, J. M.L. Articles by Koning, F. Search for Related Content PubMed PubMed Citation Articles by Tjon, J. M.L. Articles by Koning, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 10, 2008 Accepted September 1, 2008 Defective synthesis or association of T cell receptor chains underlies loss of surface T cell receptor-CD3 expression in enteropathy associated T cell lymphoma Jennifer M.L. Tjon*, Wieke H.M. Verbeek, Yvonne M.C. Kooy-Winkelaar, Binh H. Nguyen, Arno R. van der Slik, Allan Thompson, Mirjam H.M. Heemskerk, Marco W.J. Schreurs, Liesbeth H.A. Dekking, Chris J. Mulder, Jeroen van Bergen, and Frits Koning Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands Department of Gastroenterology, VU University Medical Center, Amsterdam, Netherlands Department of Hematology, Leiden University Medical Center, Leiden, Netherlands Department of Pathology, VU University Medical Center, Amsterdam, Netherlands * Corresponding author; email: j.m.l.tjon{at}lumc.nl. Enteropathy associated T cell lymphoma, an often fatal complication of celiac disease, can result from expansion of aberrant intraepithelial lymphocytes (IELs) in refractory celiac disease type II (RCD II). Aberrant IELs and lymphoma cells are intracellularly CD3+, but lack expression of the T cell receptor (TCR)-CD3 complex on the cell surface. It is unknown what causes the loss of TCR-CD3 expression. We report the isolation of a cell line from a RCD II patient with the characteristic phenotype of enteropathy associated T cell lymphoma. We demonstrate that in this cell line the TCR- and -chains as well as the CD3-, CD3-, CD3- and -chains are present intracellularly and that assembly of the CD3-, CD3- and -dimers is normal. However, dimerization of the TCR-chains and proper assembly of the TCR-CD3 complex is defective. Upon introduction of exogenous TCR-chains, but not of TCR-chains, assembly and functional cell surface expression of the TCR-CD3 complex was restored. Defective synthesis of both TCR-chains was found to underlie loss of TCR expression in similar cell lines isolated from two additional patients. (Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR-chains, resulting in loss of surface TCR-CD3 expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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