title: A novel immune evasion mechanism of LMP-1, an EBV-primary oncogene, in nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor. Viruses that are associated with malignant transformation have evolved unique mechanisms to interfere with this interaction to evade antiviral T cell responses. EBV exploits many immune evasive strategies to successfully establish a latent infection in B cells. CD8+ T cell responses to LMP-1 are generally very low and rarely detected in healthy virus carriers. Activation of the NF-kB pathway by EBV-LMP-1 leads to an upregulation of the MHC class I antigen-processing pathway. Paradoxically, LMP-1itself induces a subdominant CD8+ T cell response and appears to have evolved to avoid immune recognition. An expression of LMP-1 in human cells enhanced the trans-presentation of CD8+ T cell epitopes; however, cis-presentation of LMP-1-derived epitopes was severely impaired. Deletion of the first transmembrane domain of LMP-1, which prevented self-aggregation, significantly enhanced the cis-presentation of T cell epitopes from this protein, whereas it lost its ability to upregulate trans-presentation. These results delineate a novel mechanism of immune evasion, which renders a virally encoded oncogene inaccessible to the conventional MHC class I pathway limiting its cis-presentation.
authors.affiliation: Division of Otolaryngology, Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Takaramachi, Kanazawa, Japan. tomoy@med.kanazawa-u.ac.jp
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D002277:Carcinoma; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000821:virology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018984:Epitopes, T-Lymphocyte; D014763:Viral Matrix Proteins