Peptide-specific CD8+ T-cell evolution in vivo: response to peptide vaccination with Melan-A/MART-1.

作者: Elke Jäger , Hauni Höhn , Artje Necker , Reinhold Förster , Julia Karbach

DOI: 10.1002/IJC.10165

关键词:

摘要: Monitoring of CD8+ T-cell responses in cancer patients during peptide vaccination is essential to provide useful surrogate markers and demonstrate vaccine efficacy. We have longitudinally followed 3 melanoma who were immunized with peptides derived from Melan-A/MART-1. Recombinant HLA-A2 tetramers loaded the naturally presented Melan-A/MART-1 nonamer (AAGIGILTV) analog (ELAGIGILTV) used combination phenotypical analysis for different subsets including naive T cells, effector "true memory" cells "memory effector" based on CD45RA/RO CCR7-expression. At least a single patient, binding AAGIGILTV epitope detected naive, precursor (CD45RA+/CCR7+) ELAGIGILTV identified terminally differentiated (CD45RA+/CCR7-) subset. Molecular functional tetramer-binding revealed that receptor (TCR) repertoire was oligo/polyclonal AAGIGILTV-reactive but restricted few TCR clonotypes ELAGIGILTV-reactive prior vaccination. The reactive epitopes broadened exhibited profile cytokine release after specific stimulation: 2/3 secreted granulocyte/macrophage colony-stimulating factor (GM-CSF) interferon-gamma not interleukin-2 (IL-2) response peptides. In third IL-2 exclusively. Our results show consist associated functions. Complementary CDR3 profiles may be define most effective population induced by

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