Enhanced cytotoxicity and decreased CD8 dependence of human cancer-specific cytotoxic T lymphocytes after vaccination with low peptide dose View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-11-12

AUTHORS

Tanja Lövgren, Petra Baumgaertner, Sébastien Wieckowski, Estelle Devêvre, Philippe Guillaume, Immanuel Luescher, Nathalie Rufer, Daniel E. Speiser

ABSTRACT

In 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... »

PAGES

817-826

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00262-011-1140-1

DOI

http://dx.doi.org/10.1007/s00262-011-1140-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046433221

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22080404


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