RESUMO
In this work we eluted peptides from purified class I MHC molecules, isolated from a novel human cervical carcinoma cell line (INBL), generated in our laboratory and positive for HPV-18 infection. A fraction of these peptides was capable of stimulating T lymphocytes obtained from a donor matched for HLA-Cw4 and who was also HPV-18+. Direct N-terminal Edman degradation of these peptides, revealed the sequence (XQFPIFLQF) that matched 85% with the sequence NVFPIFLQM localized in between the 54 and 62 residues of the HPV-18 L1 protein. After stimulation with the synthetic peptide NVFPIFLQM, T lymphocytes from the donor were capable to lyse INBL cells. Our results provide evidence of the existence of naturally occurring viral epitopes presented on cervical cancer cells by the HLA-Cw4 allele, that could be useful for immunotherapy on this type of patient.
Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Papillomaviridae/imunologia , Peptídeos/imunologia , Neoplasias do Colo do Útero/virologia , Proteínas Virais/imunologia , Sequência de Aminoácidos , Antígenos Virais/química , Antígenos Virais/imunologia , Citotoxicidade Imunológica , Epitopos/imunologia , Feminino , Antígenos de Histocompatibilidade Classe I/química , Humanos , Ativação Linfocitária , Espectrometria de Massas , Dados de Sequência Molecular , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Peptídeos/química , Peptídeos/isolamento & purificação , Linfócitos T/imunologia , Células Tumorais Cultivadas , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/imunologia , Proteínas Virais/química , Proteínas Virais/isolamento & purificaçãoRESUMO
OBJECTIVE: To evaluate the effect of hematopoietic growth factors (HGF) on the proliferation of non-hematopoietic cells such as fibroblasts and epithelial cells of normal and tumoral origin. METHODS: The lymphoid factor IL-2 and the myeloid HGF assayed were IL-3, G-CSF, GM-CSF and M-CSF. The cellular proliferation was determined by measuring the amount of crystal violet dye incorporation by cells through spectrophotometry. RESULTS: All myeloid HGF tested stimulated the proliferation of cell lines 5637, CaLo and L-929. These results suggest that the stromal cells can be induced to proliferate by myeloid growth factors hinting to a bilateral interaction between these two types of cells as it is known that stromal cells in turn secrete HGF. We also observed that for the mouse fibroblastic and epithelial cells, IL-2 was unable to induce proliferation in normal cells but had a strong effect on transformed cells. Finally we discuss our observation that tumour cells responded to IL-2 as a possible mechanism for an immune escape by these cells through IL-2 depletion.