- 作者: Hsiang-Ju Lin; Jaw-Ming Cherng; Man-Shan Hung; Yiyang Sayion; Jung-Chung Lin
- 作者服務機構: 1 Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan; ; 2 Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; ; 3 Institute of Microbiology, Immunology and Molecular Medicine, Tzu Chi University College of Medicine, 701 Section 3, Chung Yang Road, Hualien, 970, Taiwan
- 中文摘要: --
- 英文摘要: Human leukocyte antigen (HLA) A2 was consistently associated with increased risk for nasopharyngeal carcinoma (NPC) in Chinese populations. Previously we have reported that an Epstein-Barr virus (EBV) strain carrying an HLA A2-restricted epitope variant of LMP-1 is prevalent in NPC in southern China and Taiwan (Lin et al., J. Gen. Virol. 85: 2023-2034, 2004). The variant has mutation selectively involved one of the two anchor residues in position 2 (125 L —> F) and an additional mutation in position 5 (129 M —> I). Functional assays of the epitope variant were carried out in the present work. The stabilization assay on T2 cells indicated that the variant peptide YFL (YFLEILWRL) prevalent in NPC binds to HLA A2 molecules less efficiently than the prototype peptide YLL (YLLEMLWRL). A dose-dependent binding of the HLA A2 molecules with added peptides was observed. In ex vivo cytotoxic T lymphocyte (CTL) assays with CD8-enriched effectors from A2-positive donors revealed that the YLL-specific CTL was able to lyse EBV-infected B cells expressing HLA A2, whereas the CTL recognition was abrogated with the peptide YFL. Cytokine (IFN-γ) responses, measured both by intracytoplasmic staining and ELISPOT assays after peptide stimulation, also indicated that the variant epitope peptide failed to give an IFN-γ response. The IFN-γ response was almost entirely restricted to those tetramer-positive cells. These results show that EBV isolates from NPC of southern China and Taiwan is dominated by an HLA A2-restricted 'epitope-loss variants' of LMP-1, which would allow the virus to resist immune recognition and may in part contribute to the prevalence of NPC in these populations.
- 中文關鍵字: --
- 英文關鍵字: A2-restricted epitopes, cytotoxic T lymphocytes, EBV, LMP-1 oncoprotein, nasopharyngeal carcinoma