IRF-4-Mediated CIITA Transcription Is Blocked by KSHV Encoded LANA to Inhibit MHC II Presentation

Peptides presentation to t cells by mhc class ii molecules is of importance in initiation of immune response to a pathogen. the level of mhc ii expression directly influences t lymphocyte activation and is often targeted by various viruses. kaposi's sarcoma-associated herpesvirus (kshv) encoded lana is known to evade mhc class i peptide processing,however,the effect of lana on mhc class ii remains unclear. here,we report that lana down-regulates mhc ii expression and presentation by inhibiting the transcription of mhc ii transactivator (ciita) promoter piii and piv in a dose-dependent manner. strikingly,although lana knockdown efficiently disrupts the inhibition of ciita transcripts from its piii and piv promoter region,the expression of hla-dqβ but no other mhc ii molecules was significantly restored. moreover,we revealed that the presentation of hla-dqβ enhanced by lana knockdown did not help lana-specific cd4+ t cell recognition of pel cells,and the inhibition of ciita by lana is independent of il-4 or ifn-γ signaling but dependent on the direct interaction of lana with irf-4 (an activator of both the piii and piv ciita promoters). this interaction dramatically blocked the dna-binding ability of irf-4 on both piii and piv promoters. thus,our data implies that lana can evade mhc ii presentation and suppress ciita transcription to provide a unique strategy of kshv escape from immune surveillance by cytotoxic t cells. © 2013 cai et al.