A Novel Immune Evasion Mechanism of LMP-1, an EBV-Primary Oncogene, in Nasopharyngeal Carcinoma

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.