CD4+ T-cell response to mitochondrial cytochrome b in human melanoma

Kui Shin Voo, Gang Zeng, Jian Bing Mu, Juhua Zhou, Xin Zhuan Su, Rongfu Wang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Mitochondrial DNA (mtDNA) is highly susceptible to mutations due to the low level of DNA repair and the presence of a high level of reactive oxygen species in the organelle. Although mtDNA mutations have been implicated in degenerating diseases, aging, and cancer, very little is known about the role of T cells in immunosurveillance for mtDNA aberrations. Here, we describe T-cell recognition of a peptide translated from an alternative open reading frame of the mitochondrial cytochrome b (cyt b) gene in melanoma cells established from a patient. To understand how the cyt b gene is transcribed and translated in tumor cells, we found that cyt b-specific CD4+ T cells only recognized protein fractions derived from cytoplasm and not from mitochondria. However, T-cell recognition of tumor cells could be inhibited by treatment of tumor cells with rhodamine 6G inhibitor, which depletes mitochondria. These findings suggest that cyt b mRNA is leaked out of the mitochondria and then translated in the cytoplasm for presentation to CD4+ T cells. The cyt b cDNAs from this patient contain highly heteroplasmic transition mutations compared with control cell lines, suggesting a compromise of mitochondrial integrity that may have contributed to melanoma induction or progression. These findings provide the first example of a mitochondrial immune target for CD4+ T cells and therefore have implications for the immunosurveillance of mitochondrial aberrations in cancer patients.

Original languageEnglish (US)
Pages (from-to)5919-5926
Number of pages8
JournalCancer research
Volume66
Issue number11
DOIs
StatePublished - Jun 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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