title: Efficient priming of CD8+ memory T cells specific for a subdominant epitope following Sendai virus infection.
abstract: The relationship between the primary effector CTL response to viral infection and the subsequent pool of memory CTL precursors (CTLp) is poorly understood. Here, we have analyzed the induction of both effector CTL and memory CTLp to dominant and subdominant epitopes following Sendai virus infection of C57BL/6 mice. A single peptide derived from the Sendai virus nucleoprotein (NP(324-332)) binds to both H-2 Kb and Db MHC class I molecules, generating both immunodominant (NP(324-332)/Kb) and subdominant (NP(324-332)/Db) epitopes. Following intranasal Sendai virus infection, NP(324-332)/Kb-specific CTL dominated the primary effector CTL response in the lung and were present at high frequency in the memory CTLp pool. In contrast, NP(324-332)/Db-specific CTL were not a detectable component of the effector response to primary Sendai virus infection. However, memory CTLp specific for this subdominant epitope were induced at frequencies approaching those of CTLp specific for the immunodominant epitope. These data indicate that memory CTLp specific for subdominant epitopes can be primed by Sendai virus infection in the absence of a detectable effector response. To determine whether CTLp memory to subdominant epitopes is functional in the context of Sendai virus infection, memory CTLp specific for a subdominant epitope were selectively primed by vaccination. These cells dominated the subsequent effector CTL response to Sendai virus infection, demonstrating that memory CTLp primed against subdominant epitopes can participate in an immune response and effectively compete with T cells specific for immunodominant epitopes. These data have implications for the development of vaccines designed to emphasize cellular immunity.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Cole
authors.forename: T L
authors.initials: TL
authors.lastname: Hogg
authors.forename: M A
authors.initials: MA
authors.lastname: Coppola
authors.forename: D L
authors.initials: DL
authors.lastname: Woodland
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides / Q000276:immunology; D018108:Respirovirus / Q000276:immunology*; D010253:Respirovirus Infections / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D006183:H-2 Antigens; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D014758:Viral Core Proteins; D014765:Viral Vaccines