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Identification of HLA-A3 and -B7-Restricted CTL Response to Hepatitis C Virus in Patients with Acute and Chronic Hepatitis C (from The Journal of Immunology 1999, 162, 1156-1164)
Bibliografi
Author:
Chang, Kyong-Mi
;
Gruener, Norbert H.
;
Southwood, Scott
;
Sidney, John
;
Pape, Gerd R.
;
Chisari, Francis V.
;
Sette, Alessandro
Topik:
HLA
;
CTL
;
Hepatitis C
;
Hepatology
;
Validation ref - 2
;
20
Bahasa:
(EN )
Penerbit:
The American Association of Immunologists, Inc.
Tempat Terbit:
Bethesda
Tahun Terbit:
1999
Jenis:
Article - diterbitkan di jurnal ilmiah internasional
Fulltext:
1156.full.pdf
(396.53KB;
0 download
)
Abstract
The inverse relationship between peripheral blood CTL responsiveness to multiple hepatitis C virus (HCV) epitopes and viral titer in patients with persistent HCV infection suggests that enhancement of the CTL response might result in viral clearance. Since several HLA-A2-restricted HCV CTL epitopes are already known, we aimed to identify CTL epitopes restricted by other HLA types in an effort to expand the epitope repertoire available for T cell-mediated therapeutic vaccine development. Scanning of 14 different HCV genome sequences for the presence of conserved peptides containing the HLA-A3 and -B7 motifs revealed 9- to 10-mer peptides that were synthesized and assayed for binding to HLA-A3, -B7 supertype molecules. Peptides with good HLAbinding affinities and cross-reactivities with at least three of five most common molecules of each supertype were tested for the ability to stimulate a memory CTL response in the peripheral blood from selected HCV-infected patients and normal seronegative donors in vitro. We identified eight HLA-A3 supertype-restricted CTL epitopes and one HLA-B7 supertype-restricted CTL epitope that were recognized by infected patients but not by healthy seronegative donors. HLA class I serotyping of 158 chronically infected patients revealed that 80% expressed one or more of HLA molecules belong to either the A2, A3, or B7 supertypes. In conclusion, the epitopes, herein identified combined with previously defined HLA-A2-restricted CTL epitopes, should be useful for the design of an ethnically unbiased, therapeutic CTL vaccine for the treatment of patients with chronic HCV infection.
[validation ref - 2, 20]
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