Ontology type: schema:ScholarlyArticle Open Access: True
2011-11-12
AUTHORSTanja Lövgren, Petra Baumgaertner, Sébastien Wieckowski, Estelle Devêvre, Philippe Guillaume, Immanuel Luescher, Nathalie Rufer, Daniel E. Speiser
ABSTRACTIn mice, vaccination with high peptide doses generates higher frequencies of specific CD8+ T cells, but with lower avidity compared to vaccination with lower peptide doses. To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund’s adjuvant. Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups. Also, CD8+ T cell differentiation and cytokine production ex vivo were similar in the two groups. Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo. In accordance, CD8+ T cell clones derived from low peptide dose-vaccinated patients showed significantly increased degranulation and stronger cytotoxicity. In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers. Furthermore, CD8+ T cell clones from low peptide dose-vaccinated patients bound CD8 binding-deficient tetramers more efficiently, suggesting that they may express higher affinity TCRs. We conclude that low peptide dose vaccination generated CD8+ T cell responses with stronger cytotoxicity and lower CD8 dependence. More... »
PAGES817-826
http://scigraph.springernature.com/pub.10.1007/s00262-011-1140-1
DOIhttp://dx.doi.org/10.1007/s00262-011-1140-1
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/22080404
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