Low frequency of cytotoxic T lymphocytes against the novel HLA-A*0201-restricted JC virus epitope VP1(p36) in patients with proven or possible progressive multifocal leukoencephalopathy.

Détails

ID Serval
serval:BIB_261072135CDD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Low frequency of cytotoxic T lymphocytes against the novel HLA-A*0201-restricted JC virus epitope VP1(p36) in patients with proven or possible progressive multifocal leukoencephalopathy.
Périodique
Journal of Virology
Auteur(s)
Du Pasquier R.A., Kuroda M.J., Schmitz J.E., Zheng Y., Martin K., Peyerl F.W., Lifton M., Gorgone D., Autissier P., Letvin N.L., Koralnik I.J.
ISSN
0022-538X[print], 0022-538X[linking]
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
77
Numéro
22
Pages
11918-11926
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
JC virus (JCV)-specific cytotoxic T lymphocytes (CTL) in peripheral blood are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (PML). However, the frequency of these cells in the peripheral blood mononuclear cells (PBMC) of PML patients is unknown. To develop a highly sensitive assay for detecting the cellular immune response against this virus, we performed a CTL epitope mapping study of JCV VP1 major capsid protein by using overlapping peptides. A novel HLA-A*0201-restricted epitope, the VP1(p36) peptide SITEVECFL, was characterized. The cellular immune response against JCV was assessed in 32 study subjects. By combining the results of the (51)Cr release assay on pooled peptides and staining with the HLA-A*0201/JCV VP1(p36) tetramer, VP1-specific CTL were detected in 10 of 11 PML survivors (91%) versus only 1 of 11 PML progressors (9%, P = 0.0003). VP1-specific CTL were also detected in two of two patients recently diagnosed with PML and in four of four human immunodeficiency virus-positive patients with possible PML. The frequency of CTL specific for the novel VP1(p36) and the previously described VP1(p100) epitopes was determined. In two patients, the frequency of CTL specific for the VP1(p36) or VP1(p100) epitopes, as determined by fresh blood tetramer staining (FBTS), ranged from 1/6,000 to 1/24,000 PBMC. A CTL sorting technique combining tetramer staining and selection with immunomagnetic beads allowed the detection of epitope-specific CTL in two cases that were determined to be negative by FBTS. The phenotype of these CTL in vivo was consistent with activated memory cells. These data suggest that, although present in low numbers, JCV-specific CTL may be of central importance in the containment of JCV spread in immunosuppressed individuals.
Mots-clé
Capsid Proteins/immunology, Epitopes, T-Lymphocyte, HLA-A Antigens/immunology, Humans, Immunophenotyping, JC Virus, Leukoencephalopathy, Progressive Multifocal/immunology, Leukoencephalopathy, Progressive Multifocal/virology, T-Lymphocytes, Cytotoxic/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:56
Dernière modification de la notice
08/05/2019 15:57
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