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Blood, 11 June 2009, Vol. 113, No. 24, pp. 6148-6152. Prepublished online as a Blood First Edition Paper on April 16, 2009; DOI 10.1182/blood-2009-02-203687. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-02-203687v1 113/24/6148    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Google Scholar Articles by Smith, C. Articles by Khanna, R. PubMed PubMed Citation Articles by Smith, C. Articles by Khanna, R. Related Collections Immunobiology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief report Discerning regulation of cis- and trans-presentation of CD8+ T-cell epitopes by EBV-encoded oncogene LMP-1 through self-aggregation Corey Smith1,*, Naohiro Wakisaka2,*, Tania Crough1, Jesse Peet1, Tomokazu Yoshizaki2, Leone Beagley1, and Rajiv Khanna1 1 Australian Centre for Vaccine Development and Tumour Immunology Laboratory, Division of Immunology, Queensland Institute of Medical Research, Brisbane, Australia; and 2 Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan Activation of the nuclear factor–B pathway by Epstein-Barr virus–encoded latent membrane protein-1 (LMP-1) leads to an up-regulation of the major histocompatibility complex class I antigen–processing pathway. Paradoxically, LMP-1 itself induces a subdominant CD8+ T-cell response and appears to have evolved to avoid immune recognition. Here we show that, although expression of LMP-1 in human cells dramatically enhanced the trans-presentation of CD8+ T-cell epitopes, cis-presentation of LMP-1–derived epitopes was severely impaired. Testing of a series of LMP-1 mutants revealed that deletion of the first transmembrane domain of LMP-1, which prevented self-aggregation, significantly enhanced cis-presentation of T-cell epitopes from this protein, whereas it lost its ability to up-regulate trans-presentation. Interestingly, we also found that cis-presentation of LMP-1 epitopes was rescued by blocking the proteasome function. Taken together, these results delineate a novel mechanism of immune evasion, which renders a virally encoded oncogene inaccessible to the conventional major histocompatibility complex class I pathway limiting its cis-presentation to effector cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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