T cell receptor usage of virus-specific CD8 cells and recognition of viral mutations during acute and persistent hepatitis B virus infection.
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.
Maini
M K
MK
Institute of Hepatology, University College London, London, GB.
Reignat
S
S
Boni
C
C
Ogg
G S
GS
King
A S
AS
Malacarne
F
F
Webster
G J
GJ
Bertoletti
A
A
D000208:Acute Disease; D000328:Adult; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell