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
Receptors for the Fc fragment of immunoglobulins G (Fc gamma R) belong to the immunoglobulin superfamily and are expressed on different cell types. These receptors are classified in three different groups (Fc gamma RI, Fc gamma RII and Fc gamma RIII) depending upon their molecular weight, affinity and specificity for their ligands. In addition to all these differences, genetic polymorphisms induce the expression of several isoforms, making the Fc gamma R a heterogeneous group. The Fc gamma Rs have been the subject of intense research on their gene organization, biochemical and structural properties. It has also been established that the Fc gamma R play an important functional role on the regulation of the biological responses that are triggered during inflammatory stages (e.g. an infection), as they link the cellular and humoral branches of the immune response. In this article we give examples of the participation of Fc gamma R on the regulation of the immune response as well as the activation of intracellular mechanisms (transduction signals) after the crosslinking of Fc gamma R by antigen-antibody complexes. The effect of cytokines and growth factors on the regulation of Fc gamma R expression is also described. We discuss the importance of the possible use of some of these molecules to control the expression of Fc gamma R in some clinical situations where alterations on their expression are associated with some diseases. Finally, we analyze the role of Fc gamma R as the point of entry of infectious agents such as HIV.