title: Impaired memory CD8 T cell responses against an immunodominant retroviral cryptic epitope.
abstract: The immunodominant cryptic epitope SYNTGRFPPL, encoded within open reading frame 2 of the LP-BM5 retroviral gag gene, is critical for protection against retroviral-induced pathogenesis. The goal of this study was to dissect the memory response against this unique immunodominant cryptic epitope. Unlike the protective acute effector population of SYNTGRFPPL-specific CD8 T cells, long-lived SYNTGRFPPL-specific CD8 T cells lacked the ability to protect susceptible mice infected with LP-BM5 retrovirus. Compared to memory CD8 T cells against a conventional epitope with similar MHC-I specificity, primed and restimulated using similar conditions, long-lived SYNTGRFPPL-specific CD8 T cells were impaired in their ability to recall against antigen, with reduced cytolytic capabilities and cytokine production. Since similar priming and restimulation regimes were utilized to generate each effector CD8 T cell population, this study has potentially broad implications with regard to the selection criteria of potent, highly conserved cryptic epitopes for use in epitope-based vaccines.
authors.affiliation: Department of Microbiology and Immunology and Norris Cotton Cancer Center, Dartmouth Medical School, One Medical Center Drive, Borwell Bldg, Lebanon, NH 03756, USA.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Rutkowski
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Stevens
authors.forename: William R
authors.initials: WR
authors.lastname: Green
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D012190:Retroviridae / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology*
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D016056:Immunodominant Epitopes