RT Journal Article
T1 Genome-wide characterization of a viral cytotoxic T lymphocyte epitope repertoire
A1 Zhong, Weimin
A1 Reche Gallardo, Pedro Antonio
A1 Lai, Char-Chang
A1 Reinhold, Bruce
A1 Reinherz, Ellis L
AB A genome-wide search using major histocompatibility complex (MHC) class I binding and proteosome cleavage site algorithms identified 101 influenza A PR8 virus-derived peptides as potential epitopes for CD8+ T cell recognition in the H-2b mouse. Cytokine-based flow cytometry, ELISPOT, and cytotoxic T lymphocyte assays reveal that 16 are recognized by CD8+ T cells recovered directly ex vivo from infected animals, accounting for greater than 70% of CD8+ T cells recruited to lung after primary infection. Only six of the 22 highest affinity MHC class I binding peptides comprise cytotoxic T lymphocyte epitopes. The remaining non-immunogenic peptides have equivalent MHC affinity and MHC-peptide complex half-lives, eliciting T cell responses when given in adjuvant and with T cell receptor-ligand avidity comparable with their immunogenic counterparts. As revealed by a novel high sensitivity nanospray tandem mass spectrometry methodology, failure to process those predicted epitopes may contribute significantly to the absent response. These results have important implications for rationale design of CD8+ T cell vaccines.
PB American Society for Biochemistry and Molecular Biology
SN 0021-9258
YR 2003
FD 2003
LK https://hdl.handle.net/20.500.14352/58244
UL https://hdl.handle.net/20.500.14352/58244
LA eng
DS Docta Complutense
RD 8 abr 2025