生物
CD8型
MHC I级
表位
细胞毒性T细胞
抗原
主要组织相容性复合体
爱泼斯坦-巴尔病毒
T细胞
分子生物学
病毒学
抗原呈递
细胞生物学
病毒
体外
免疫系统
免疫学
遗传学
作者
Steven P. Lee,Jill M. Brooks,Hatim Al-Jarrah,Wendy A. Thomas,Tracey A. Haigh,Graham S. Taylor,Sibille Humme,Aloys Schepers,Wolfgang Hammerschmidt,John L. Yates,Alan B. Rickinson,Neil Blake
摘要
The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I–restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon γ release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter–dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies.
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