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Articles by Carla Oseroff
Total Records ( 2 ) for Carla Oseroff
  Erika Assarsson , Huynh -Hoa Bui , John Sidney , Qing Zhang , Jean Glenn , Carla Oseroff , Innocent N. Mbawuike , Jeff Alexander , Mark J. Newman , Howard Grey and Alessandro Sette
  Continuing antigenic drift allows influenza viruses to escape antibody-mediated recognition, and as a consequence, the vaccine currently in use needs to be altered annually. Highly conserved epitopes recognized by effector T cells may represent an alternative approach for the generation of a more universal influenza virus vaccine. Relatively few highly conserved epitopes are currently known in humans, and relatively few epitopes have been identified from proteins other than hemagglutinin and nucleoprotein. This prompted us to perform a study aimed at identifying a set of human T-cell epitopes that would provide broad coverage against different virus strains and subtypes. To provide coverage across different ethnicities, seven different HLA supertypes were considered. More than 4,000 peptides were selected from a panel of 23 influenza A virus strains based on predicted high-affinity binding to HLA class I or class II and high conservancy levels. Peripheral blood mononuclear cells from 44 healthy human blood donors were tested for reactivity against HLA-matched peptides by using gamma interferon enzyme-linked immunospot assays. Interestingly, we found that PB1 was the major target for both CD4+ and CD8+ T-cell responses. The 54 nonredundant epitopes (38 class I and 16 class II) identified herein provided high coverage among different ethnicities, were conserved in the majority of the strains analyzed, and were consistently recognized in multiple individuals. These results enable further functional studies of T-cell responses during influenza virus infection and provide a potential base for the development of a universal influenza vaccine.
  Courtney Dow , Carla Oseroff , Bjoern Peters , Courtney Nance-Sotelo , John Sidney , Michael Buchmeier , Alessandro Sette and Bianca R. Mothe
  Activation of CD4+ T cells helps establish and sustain other immune responses. We have previously shown that responses against a broad set of nine CD4+ T-cell epitopes were present in the setting of lymphocytic choriomeningitis virus (LCMV) Armstrong infection in the context of H-2d. This is quite disparate to the H-2b setting, where only two epitopes have been identified. We were interested in determining whether a broad set of responses was unique to H-2d or whether additional CD4+ T-cell epitopes could be identified in the setting of the H-2b background. To pursue this question, we infected C57BL/6 mice with LCMV Armstrong and determined the repertoire of CD4+ T-cell responses using overlapping 15-mer peptides corresponding to the LCMV Armstrong sequence. We confirmed positive responses by intracellular cytokine staining and major histocompatibility complex (MHC)-peptide binding assays. A broad repertoire of responses was identified, consisting of six epitopes. These epitopes originate from the nucleoprotein (NP) and glycoprotein (GP). Out of the six newly identified CD4+ epitopes, four of them also stimulate CD8+ T cells in a statistically significant manner. Furthermore, we assessed these CD4+ T-cell responses during the memory phase of LCMV Armstrong infection and after infection with a chronic strain of LCMV and determined that a subset of the responses could be detected under these different conditions. This is the first example of a broad repertoire of shared epitopes between CD4+ and CD8+ T cells in the context of viral infection. These findings demonstrate that immunodominance is a complex phenomenon in the context of helper responses.
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