Identification of CD4+ T cell epitopes in HLA-DRB1*1501 subjects after H5N1 avian flu vaccination

• Main Authors: Ling Yao, 姚菱
• Other Authors: Jason C. Huang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/rhxskq

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 97 === The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Despite of the physical protections such as wearing masks and washing hands, vaccination is still the most effective method to protect humans against influenza epidemics or even pandemics. After vaccination, antigen-specific T helper cells play an important role in coordinating the immune system against virus infection. Validating the specific CD4+ T cells response should provide information on the efficacy of vaccines. Here, we performed a comprehensive in vitro analysis of antigen-specific CD4+ T cell responses to overlapping peptides spanning the HA1 protein of influenza A/Viet Nam/1203/04 (H5N1) in healthy individuals who were inoculated with the GlaxoSmithKline H5N1 adjuvanted pre-pandemic vaccine, Prepandrix™. After in vitro expansion of T cells, we used intracellular cytokine staining to identify the potential immunodominant epitopes and utilized MHC class II tetramer for further confirmation of the antigen-specific CD4+ T cells. The results showed that the HA148-162, HA155-169, HA253-267, HA260-274, HA267-281, and HA309-323 peptides of A/Viet Nam/1203/04 virus can elicit significant cytokine response in immunized subjects carrying HLA-DRB1*1501 which is among the top three prevalent HLA alleles in Taiwan. Among the six epitopes, only HA267-281 was an immunodominant epitope which elicited strong cellular immune response in specific T cells and those T cells could be stained by peptide-load DR1501 tetramer. Furthermore, the unique HA267-281 response was barely detected in non-vaccinated DR1501 individuals. In addition, the HA267-281 epitope is unique for the H5N1 strain but highly conserved among recently cirulating H5N1 clades in Asia. Collectively, combining the results with MHC tetramer technology, we suggest that H5N1 strain-specific HA267-281 epitope should represent an important marker for monitoring the efficacy of vaccination or as a component of candidate vaccine peptides.