Genome-wide characterization of a viral cytotoxic T lymphocyte epitope repertoire



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Zhong, Weimin and Reche, Pedro A and Lai, Char-Chang and Reinhold, Bruce and Reinherz, Ellis L (2003) Genome-wide characterization of a viral cytotoxic T lymphocyte epitope repertoire. The Journal of Biological Chemistry, 278 (46). pp. 45135-44. ISSN 0021-9258

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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.

Item Type:Article
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Microbiology
Sciences > Computer science > Bioinformatics
Medical sciences > Biology > Molecular biology
ID Code:9337
Deposited On:06 Aug 2009 10:19
Last Modified:13 Dec 2018 12:48

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