Inefficient Recognition of Autologous Viral Sequences by Intrahepatic Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in Chronically Infected Subjects
Identifieur interne : 003B54 ( Main/Exploration ); précédent : 003B53; suivant : 003B55Inefficient Recognition of Autologous Viral Sequences by Intrahepatic Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in Chronically Infected Subjects
Auteurs : Vicki M. Giuggio ; Herbert L. Bonkovsky ; Jesse Smith ; Alan L. RothmanSource :
- Virology [ 0042-6822 ] ; 1998.
English descriptors
- Teeft :
- Allogeneic, Allogeneic pbmcs, Allogeneic target cells, Amino, Amino acids, Antisense primers, Assay, Autologous, Autologous peptide sequence, Autologous sequence, Binding motif, Bulk culture, Cdna, Chromium release assay, Chromium release assays, Chronic hepatitis, Clone, Complete medium, Cytotoxic, Effector cells, Epitope, Genotype, Hepatitis, Hmycr1, Inefficient recognition, Intrahepatic, Koziel, Lymphocyte, Lyse, Lyse target cells, Lysis, Pbmcs, Peptide, Peptide concentrations, Primer, Prototype, Prototype sequence, Rdwahngl, Recombinant vaccinia virus, Target cells, Ummc, Vaccinia, Viral, Viral cdna, Virus infection.
Abstract
Abstract: Cytotoxic T lymphocytes (CTL) capable of recognizing prototype hepatitis C virus (HCV) sequences have been shown to localize to the liver in chronically infected individuals, where they are thought to influence hepatic inflammation and viral replication. We isolated three intrahepatic CD8+CTL clones from two individuals with chronic HCV infection and compared the recognition of prototype and autologous HCV sequences. These CTL recognized epitopes within the NS2 (amino acids 957–964) or NS3 (amino acids 1402–1410 and 1406–1415) proteins in the context of HLA B37, B8, or A2.1, respectively. The corresponding predominant autologous HCV sequences (SDWAANGL, ELAAKLVGL, and ALRGMGVNAV, respectively) differed from the HCV-1 sequences used for screening (RDWAHNGL, ELAAKLVAL, and KLVALGINAV, respectively) at one to five residues. For each CTL clone, recognition of the autologous HCV sequence required significantly higher peptide concentrations than did recognition of the HCV-1 sequence; for two of the clones, recognition was minimal or absent at peptide concentrations as high as 25 μM. These data show that intrahepatic HCV-specific CD8+CTL clones can be relatively inefficient at recognizing autologous viral epitopes. Inefficient recognition of autologous HCV sequences should influence the interpretation of data generated using prototype HCV sequences and might have implicationsin vivo.
Url:
DOI: 10.1006/viro.1998.9401
Affiliations:
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We isolated three intrahepatic CD8+CTL clones from two individuals with chronic HCV infection and compared the recognition of prototype and autologous HCV sequences. These CTL recognized epitopes within the NS2 (amino acids 957–964) or NS3 (amino acids 1402–1410 and 1406–1415) proteins in the context of HLA B37, B8, or A2.1, respectively. The corresponding predominant autologous HCV sequences (SDWAANGL, ELAAKLVGL, and ALRGMGVNAV, respectively) differed from the HCV-1 sequences used for screening (RDWAHNGL, ELAAKLVAL, and KLVALGINAV, respectively) at one to five residues. For each CTL clone, recognition of the autologous HCV sequence required significantly higher peptide concentrations than did recognition of the HCV-1 sequence; for two of the clones, recognition was minimal or absent at peptide concentrations as high as 25 μM. These data show that intrahepatic HCV-specific CD8+CTL clones can be relatively inefficient at recognizing autologous viral epitopes. Inefficient recognition of autologous HCV sequences should influence the interpretation of data generated using prototype HCV sequences and might have implicationsin vivo.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Bonkovsky, Herbert L" sort="Bonkovsky, Herbert L" uniqKey="Bonkovsky H" first="Herbert L." last="Bonkovsky">Herbert L. Bonkovsky</name><name sortKey="Giuggio, Vicki M" sort="Giuggio, Vicki M" uniqKey="Giuggio V" first="Vicki M." last="Giuggio">Vicki M. Giuggio</name><name sortKey="Rothman, Alan L" sort="Rothman, Alan L" uniqKey="Rothman A" first="Alan L." last="Rothman">Alan L. Rothman</name><name sortKey="Smith, Jesse" sort="Smith, Jesse" uniqKey="Smith J" first="Jesse" last="Smith">Jesse Smith</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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