Down-regulation of Human MHC Class II by Epstein-Barr virus Latent Membrane Protein 2A

• Main Authors: Ju-Yin Lin, 林如愔
• Other Authors: 蔡錦華
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/24339185028502842483

碩士 === 國立臺灣大學 === 微生物學研究所 === 98 === The presentation of peptides to CD4+ T cells by MHC class II molecules is of critical importance in specific recognition to a pathogen by the immune system. The level of MHC class II directly influences T lymphocyte activation. Activated CD4+ T cells can produce antiviral cytokines or co-ordinate antiviral immune responses. Viruses escape detection by CD4+ T cells by at least two mechanisms, inhibiting the expression of MHC class II genes and the antigen presentation pathway. Epstein-Barr virus (EBV) is an oncogenic gamma-herpesvirus that persistently infects over 92% of the human population. The previous studies have shown that several EBV-encoded gene products can disrupt MHC class II function. Using EBV- immortalized B cells (lymphoblastoid cell line) as model system, we found that the expression of MHC class II is repressed in the present of EBV. The aim of this study was to identify the possible mechanisms of the down-regulation of MHC class II expression by EBV. The data in the present study demonstrated that ectopic expression of LMP2A can inhibit the constitutive expression of MHC class II and CIITA in B cell lines. The down-regulated mRNA level of MHC class II and CIITA was correlated to the suppressed level of PU.1, one of the transcription factors of CIITA, in the present of LMP2A. With LMP2A mutant constructs, we displayed that the ITAM motif could be responsible for the repression effect on MHC class II expression. On the other hand, by si-LMP2A expression in LCLs, we found the expression levels of MHC class II, CD74, CIITA and PU.1 were reversed. Taking together, LMP2A might suppress MHC class II expression through PU.1-CIITA pathway, and the ITAM motif on N-terminal tail of LMP2A could be responsible for it.