Epitopes described in "Multiple distinct forms of CD8+ T cell cross-reactivity and specificities revealed after 2009 H1N1 influenza A virus infection in mice."

Article Authors:Hailong Guo; David J Topham
Article Title:Multiple distinct forms of CD8+ T cell cross-reactivity and specificities revealed after 2009 H1N1 influenza A virus infection in mice.
Reference Detail
Reference ID:1025163
Abstract:Influenza primed mice are protected against lethal infection with H1N1 A/CA/04/E3/09 virus, and T depletion and serum transfer studies suggest a T-dependent mechanism. We therefore set out to investigate the quality of the cross-reactive T cell response to CA/E3/09 in mice primed with H3N2 influenza A/Hong Kong/X31 virus. Sequences of the immunodominant nucleoprotein (NP) NP366-374 and acid polymerase (PA) PA224-233 CD8 epitopes from X31 each differ from the CA/E3/09 virus by one amino acid: an M371V substitution at position 6 of the NP peptide, and an S224P substitution at position 1 of the PA peptide, raising questions about the role of these epitopes in protection. PA224-233 peptides from either virus could elicit IFN- spot forming cells from mice infected with X31, indicating cross-reactivity of these two peptides. However, no T cell responses to either PA224-233 peptide were detectable after primary CA/E3/09 infection, suggesting it is cryptic in this virus. In contrast, primary responses to the NP366 peptides were detectable after infection with either virus, but did not cross-react in vitro. Similarly, H2-D(b) tetramers of each NP epitope stained CD8+ T cells from each respective virus infection, but did not obviously cross-react. Early after lethal CA/E3/09 challenge, X31 primed mice had enhanced IFN- responses toward both NP366 peptides, as well as recall responses to a set of subdominant NP and PA peptides not detectable after primary X31 infection alone. Furthermore, dual-tetramer staining revealed an expanded population of CD8 T cells reactive to both NP366 variant peptides also not seen after the priming infection alone. These observations demonstrate unusual CD8+ T cell cross-reactivity and specificity are elicited after primary and secondary CA/E3/09 influenza virus infections.
Affiliations:Center for Infectious Diseases and Vaccine Immunology, Rochester General Hospital Research Institute, Rochester, New York, United States of America. jackguo1234@yahoo.com.
Reference Type:Literature
PubMed ID:23029425
Journal:PLoS One
Journal Volume:7
Article Pages:e46166
Journal ISSN:1932-6203
Article Chemical List:Antigens, Viral;Epitopes, T-Lymphocyte;Nucleoproteins;Oligopeptides;DNA-Directed DNA Polymerase
Article MeSH List:Amino Acid Substitution; Animals; Antigens, Viral(administration & dosage; genetics; immunology); CD8-Positive T-Lymphocytes(cytology; immunology); Cross Protection; Cross Reactions; DNA-Directed DNA Polymerase(genetics; immunology); Epitopes, T-Lymphocyte(genetics; immunology); Humans; Immunologic Memory; Influenza A Virus, H1N1 Subtype(genetics; immunology); Influenza A Virus, H3N2 Subtype(genetics; immunology); Mice; Nucleoproteins(administration & dosage; genetics; immunology); Oligopeptides(administration & dosage; genetics; immunology); Orthomyxoviridae Infections(immunology; prevention & control; virology); T-Cell Antigen Receptor Specificity
Curation Last Updated:2015-07-30 20:46:25