Conjugation of Latent Membrane Protein (LMP)-2 Epitope to Gold Nanoparticles as Highly Immunogenic Multiple Antigenic Peptides for Induction of Epstein−Barr Virus-Specific Cytotoxic T-Lymphocyte

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• 作者：Wai-Hung Cheung ; Vera Sau-Fong Chan ; Heung-Wing Pang ; Man-Kin Wong ; Zhi-Hong Guo ; Paul Kwong-Hang Tam ; Chi-Ming Che ; Chen-Lung Lin ; Wing-Yiu Yu
• 刊名：Bioconjugate Chemistry
• 出版年：2009
• 出版时间：January 21, 2009
• 年：2009
• 卷：20
• 期：1
• 页码：24-31
• 全文大小：279K
• 年卷期：v.20,no.1(January 21, 2009)
• ISSN：1520-4812

文摘

Nasopharyngeal carcinoma is a neoplasm with a high incidence in Southeast Asia, and it is strongly associated with Epstein−Barr virus (EBV) activation involving the expression of a weakly immunogenic protein, namely, latent membrane protein (LMP)-2. Previous immunological studies already identified the human leukocyte antigen (HLA)-A11 restricted peptide epitope (SSCSSCPLSK) in the LMP-2 antigen. In this work, we prepared gold nanoparticle (AuNP)−peptide conjugate 1 by treating the nanoparticles with the N-cysteinated LMP-2 epitope. The AuNP−peptide conjugates have been characterized by TEM (15−24 nm in diameter) and UV−vis spectroscopy (surface plasmon resonance absorption band at λ_max = 520 nm). In the presence of a CALNN capping peptide, the AuNP−peptide conjugates are stable in solution without aggregation at room temperature for at least 48 h. By ELIspot studies, AuNP−peptide conjugate 1 was found to elicit a significantly stronger INF-γ response [number of spot forming cells (SPC) = 727 ± 198] from peripheral blood mononuclear cells of healthy HLA-A11 donors when compared to that induced by the unconjugated LMP-2 peptides (SFC = 73 ± 28). Further studies showed that dendritic cells treated with conjugate 1 can effect CD8+ T-cell activation leading to epitope-specific cytotoxic T lymphocyte killing responses in vitro.