Hepatitis C Clinical Trial
Official title:
Identification of HCV Specific T Cells Using Tetramer Technology - TETRA Study
Nearly 175 million people worldwide are infected by Hepatitis C Virus (HCV), close to 3% of
the global population. Contrary to other chronic infections such as HIV, clearance of HCV is
possible. While much is now known about the response to treatment in chronic HCV patients,
the fact that acute HCV infection is typically asymptomatic (~80% of patients show no
clinical signs) has made it challenging to define the mechanisms involved in spontaneous
clearance.
Immune protection against HCV is thought to be largely dependent upon the CD8 T cell
response. Therefore using the latest T cell detection technology the investigators will
develop a panel of tetramers specific for all potential HCV epitopes. To produce the
tetramers the investigators will utilize HLA ligand exchange technology which allows the
production of very large collections of peptide-HLA multimers for T cell staining. The
investigators have already performed a large scale identification of HCVg1 and HCVg4 CD8 T
cell epitopes using published viral sequences and algorithm prediction databases. Using this
information the investigators are currently in the process of developing collections of
peptide-HLA multimers for T cell staining. Therefore the investigators require large
lymphocyte pools from HCV+ patients to test both the sensitivity and accuracy of each
tetramer on the CD3+CD8+ T cells.
The investigators wish to examine cells from patients infected with HCV g1 and HCV g4 to be
able to test and compare the frequency of possible conserved epitopes present in both HCVg1
and HCVg4 infections. Once developed this technique will allow us to examine all
virus-specific CD8 T cells present in patients with acute or chronic disease, and on smaller
quantities of blood. The development of these technologies will also allow us to tailor such
future diagnostic tests to local populations where a viral subspecies is prevalent; for
example using North-African HLA alleles for HCVg4 epitopes.
The work carried out using such assays will provide important immunological correlates of
viral clearance that will impact vaccine design for HCV infections. Finally, the
identification of protective CD8 T cells specific for HCV may allow new diagnostic tools
with predictive powers of disease progression that can be used on any flow cytometer
machine.
n/a
Observational Model: Case-Only, Time Perspective: Prospective
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