Immunogenicity of constitutively active V599EBRaf

Mads Hald Andersen, Joachim Fensterle, Selma Ugurel, Sine Reker Hadrup, Roland Houben, Per Guldberg, Thomas G. Berger, Dirk Schadendorf, Uwe Trefzer, Eva B. Bröcker, Per Thor Straten, Ulf R. Rapp, Jürgen C. Becker

Research output: Contribution to journalJournal articleResearchpeer-review


Activating BRAF somatic missense mutations within the kinase domain are present in 60-66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.
Original languageEnglish
JournalCancer Research
Issue number15
Pages (from-to)5456-5460
Number of pages5
Publication statusPublished - 2004
Externally publishedYes


  • Cancer Research
  • Oncology
  • B Raf kinase
  • epitope
  • gene product
  • glutamic acid
  • HLA B antigen
  • mutant protein
  • unclassified drug
  • valine
  • amino acid substitution
  • antigen recognition
  • article
  • braf gene
  • cell clone
  • cell selection
  • cellular immunity
  • clonal selection
  • controlled study
  • cytotoxic T lymphocyte
  • gene
  • genotype
  • host
  • human
  • human cell
  • immunogenicity
  • immunoselection
  • major histocompatibility complex restriction
  • melanoma
  • melanoma cell
  • metastasis
  • missense mutation
  • priority journal
  • somatic mutation
  • tumor bearing host
  • tumor growth
  • wild type
  • Disease Progression
  • Epitopes
  • Genotype
  • HLA-B Antigens
  • Humans
  • Melanoma
  • Mutation, Missense
  • Peptide Fragments
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-raf
  • Skin Neoplasms
  • T-Lymphocytes, Cytotoxic


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