tetano
Editor, Senior Moderator
J Virol. 2014 Jul 30. pii: JVI.01631-14. [Epub ahead of print]
Immunodominant CD4+ T-cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein.
Chen L1, Zanker D2, Xiao K2, Wu C3, Zou Q3, Chen W4.
Author information
Abstract
Antigen-specific CD4+ T cells are essential for effective virus-specific host responses, with recent human challenge studies (in volunteers) establishing their importance for influenza A viruses (IAV)-specific immunity. However, while many IAV CD4+ T cell epitopes have been identified, few are known to stimulate immunodominant CD4+ T cell responses. Moreover, much remains unclear concerning the major antigen(s) responded to by the human CD4+ T cells and the extent and magnitude of these responses. We initiated a systematic screen of immunodominant CD4+ T cell responses to IAV in healthy individuals. Using in vitro expanded multi-specificity IAV-specific T cell lines and individual IAV protein antigens produced by recombinant vaccinia viruses, we found that the internal Matrix protein 1 (M1) and Nucleoprotein (NP) were the immunodominant targets of CD4+ T cell responses. Ten epitopes derived from M1 and NP were definitively characterized. Furthermore, epitope sequence conservation analysis established that immunodominance correlated with an increased frequency of mutations, reflecting that these prominent epitopes are under greater selective pressure. Such evidence that particular CD4+ T cells are important for protection/recovery is of value for the development of novel IAV vaccines, and for our understanding of differential susceptibility profiles to these major pathogens.
IMPORTANCE STATEMENT:
Influenza virus causes half a million deaths annually. CD4+ T cell responses have been shown to be important for influenza protection and recovery. CD4+ T cell responses are also critical for efficient CD8+ T cell response and antibody response. As immunodominant T cells generally play more important role, characterizing these immunodominant responses is critical for influenza vaccine development. We show here that the internal Matrix protein 1 (M1) and Nucleoprotein (NP), rather than the surface proteins reported previously, are the immunodominant targets of CD4+ T cell responses. Interestingly, these immunodominant epitope regions accumulated many mutations overtime, which likely indicates increased immune pressure. These findings have significant implications for the design of T cell based influenza vaccines.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25078703
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25078703
Immunodominant CD4+ T-cell Responses to Influenza A Virus in Healthy Individuals Focus on Matrix 1 and Nucleoprotein.
Chen L1, Zanker D2, Xiao K2, Wu C3, Zou Q3, Chen W4.
Author information
Abstract
Antigen-specific CD4+ T cells are essential for effective virus-specific host responses, with recent human challenge studies (in volunteers) establishing their importance for influenza A viruses (IAV)-specific immunity. However, while many IAV CD4+ T cell epitopes have been identified, few are known to stimulate immunodominant CD4+ T cell responses. Moreover, much remains unclear concerning the major antigen(s) responded to by the human CD4+ T cells and the extent and magnitude of these responses. We initiated a systematic screen of immunodominant CD4+ T cell responses to IAV in healthy individuals. Using in vitro expanded multi-specificity IAV-specific T cell lines and individual IAV protein antigens produced by recombinant vaccinia viruses, we found that the internal Matrix protein 1 (M1) and Nucleoprotein (NP) were the immunodominant targets of CD4+ T cell responses. Ten epitopes derived from M1 and NP were definitively characterized. Furthermore, epitope sequence conservation analysis established that immunodominance correlated with an increased frequency of mutations, reflecting that these prominent epitopes are under greater selective pressure. Such evidence that particular CD4+ T cells are important for protection/recovery is of value for the development of novel IAV vaccines, and for our understanding of differential susceptibility profiles to these major pathogens.
IMPORTANCE STATEMENT:
Influenza virus causes half a million deaths annually. CD4+ T cell responses have been shown to be important for influenza protection and recovery. CD4+ T cell responses are also critical for efficient CD8+ T cell response and antibody response. As immunodominant T cells generally play more important role, characterizing these immunodominant responses is critical for influenza vaccine development. We show here that the internal Matrix protein 1 (M1) and Nucleoprotein (NP), rather than the surface proteins reported previously, are the immunodominant targets of CD4+ T cell responses. Interestingly, these immunodominant epitope regions accumulated many mutations overtime, which likely indicates increased immune pressure. These findings have significant implications for the design of T cell based influenza vaccines.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25078703
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25078703