CD4+ T-cell response to mitochondrial cytochrome B in human melanoma.
Cancer Res
; 66(11): 5919-26, 2006 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-16740732
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.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
/
Epitopos de Linfócito T
/
Citocromos b
/
Melanoma
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos