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T cells specific for a single viral epitope, but using different T cell receptors, should have flexibility in their epitope recognition to protect the infected host against the emergence of viral escape mutants. Therefore, polyclonality of the hepatitis B virus (HBV)-specific cytotoxic T lymphocyte response has been hypothesized to be a major determinant in the control of infection. We analyzed the Vbeta chain composition of the core 18-27-specific CD8 cells in acute and persistently HBV-infected patients using HLA-A2 tetrameric complexes and a panel of Vbeta antibodies. Different T cell receptors were utilized by core 18-27-specific CD8 cells both in patients with acute and chronic infection. The functional ability of these epitope-specific T cells to respond to potential viral mutations was then tested. The polyclonal HBV-specific CD8 response present in patients with acute hepatitis displayed a limited efficiency to recognize mutations introduced within the epitope. The ability of core 18-27-specific CD8 to tolerate epitope mutations was found only during persistent HBV infection. The data suggest that although a clonally heterogeneous CD8 response can be largely inhibited by the occurrence of single epitope mutations in primary HBV infection, preferential selection of T cells able to counteract the emergence of viral mutations can occur during persistent infection.

Original publication

DOI

10.1002/1521-4141(200011)30:11<3067::AID-IMMU3067>3.0.CO;2-L

Type

Journal article

Journal

Eur J Immunol

Publication Date

11/2000

Volume

30

Pages

3067 - 3078

Keywords

Acute Disease, Adult, Antigens, Viral, CD8-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Epitopes, Hepatitis B, Hepatitis B, Chronic, Humans, Mutation, Receptors, Antigen, T-Cell