title: Multiple distinct forms of CD8+ T cell cross-reactivity and specificities revealed after 2009 H1N1 influenza A virus infection in mice.
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-γ 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-γ 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.
authors.affiliation: Center for Infectious Diseases and Vaccine Immunology, Rochester General Hospital Research Institute, Rochester, New York, United States of America. jackguo1234@yahoo.com
authors.forename: Hailong
authors.initials: H
authors.lastname: Guo
authors.forename: David J
authors.initials: DJ
authors.lastname: Topham
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D056738:Cross Protection; D003429:Cross Reactions; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D051379:Mice; D009698:Nucleoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D009842:Oligopeptides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D037182:T-Cell Antigen Receptor Specificity
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D009698:Nucleoproteins; D009842:Oligopeptides; D004259:DNA-Directed DNA Polymerase