title: Selective expansion of cross-reactive CD8(+) memory T cells by viral variants.
abstract: The role of memory T cells during the immune response against random antigenic variants has not been resolved. Here, we show by simultaneous staining with two tetrameric major histocompatibility complex (MHC)-peptide molecules, that the polyclonal CD8(+) T cell response against a series of natural variants of the influenza A nucleoprotein epitope is completely dominated by infrequent cross-reactive T cells that expand from an original memory population. Based on both biochemical and functional criteria, these cross-reactive cytotoxic T cells productively recognize both the parental and the mutant epitope in vitro and in vivo. These results provide direct evidence that the repertoire of antigen-specific T cells used during an infection critically depends on prior antigen encounters, and indicate that polyclonal memory T cell populations can provide protection against a range of antigenic variants.
authors.affiliation: Department of Immunology, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands.
authors.forename: J B
authors.initials: JB
authors.lastname: Haanen
authors.forename: M C
authors.initials: MC
authors.lastname: Wolkers
authors.forename: A M
authors.initials: AM
authors.lastname: Kruisbeek
authors.forename: T N
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D003429:Cross Reactions / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D007114:Immunization; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics* / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D000939:Epitopes; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins