Decreased EBNA-1-specific CD8+ T cells in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma.

Abstract

The Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) is potentially a universal target for immune recognition of EBV-infected normal or malignant cells. EBNA-1-specific CD8+ T-cell responses have been assessed against a few epitopes presented on a limited number of HLA class I alleles. We now assess CD8+ T-cell responses to a complete panel of EBNA-1 peptides in an HLA-characterized population. We detected EBNA-1-specific CD8+ T cells in 10 of 14 healthy donors by analysis of peripheral blood mononuclear cells and EBV-specific T-cell lines. The frequent detection of CD8+ T-cell responses was confirmed by mapping EBNA-1 epitopes and demonstrating HLA class I presentation to CD8+ T cells in 6 of 6 donors, including 2 new EBNA-1 epitopes presented by HLA A0206 and A6802. Importantly, EBNA-1-specific CD8+ T cells were significantly less frequent in EBV-specific T-cell lines from patients with EBV-associated nasopharyngeal carcinoma (3 out of 22, P = 0.0003), whereas the frequency of LMP2-specific responses (14 out of 22) was not significantly different from healthy donors (11 out of 14). EBNA-1-specific CD8+ T-cell responses were rescued in approximately half of nasopharyngeal carcinoma patients by peptide and cytokine stimulation of peripheral blood mononuclear cells, suggesting these EBNA-1-specific CD8+ T cells were functionally defective in their response to EBV-infected cells. These results indicate that humans normally mount a significant EBNA-1-specific CD8+ T-cell response to EBV infection, but the immune response to this tumor antigen has been significantly altered in nasopharyngeal carcinoma patients. Overcoming this defect in EBV-specific immunity may prevent or enhance treatment of EBV-associated nasopharyngeal carcinoma.

• Authors: Mark H Fogg, Lori J Wirth, Marshall Posner, Fred Wang
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 9 Pg. 3318-23 (Mar 03 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19211798 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• EBV-associated membrane antigen, Epstein-Barr virus
• Epitopes
• Epstein-Barr Virus Nuclear Antigens
• Viral Matrix Proteins
• EBV-encoded nuclear antigen 1

Topics

• CD8-Positive T-Lymphocytes (immunology)
• Case-Control Studies
• Epitopes (immunology)
• Epstein-Barr Virus Infections (blood, complications, immunology, virology)
• Epstein-Barr Virus Nuclear Antigens (immunology)
• Health
• Herpesvirus 4, Human (immunology)
• Humans
• Nasopharyngeal Neoplasms (blood, etiology, immunology, virology)
• Substrate Specificity
• Viral Matrix Proteins (immunology)