Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection.
Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically "tolerant" since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.
Reignat
Stephanie
S
Institute of Hepatology, University College London, London WC1 E6HX, United Kingdom.
Webster
George J M
GJ
Brown
David
D
Ogg
Graham S
GS
King
Abigail
A
Seneviratne
Suranjith L
SL
Dusheiko
Geoff
G
Williams
Roger
R
Maini
Mala K
MK
Bertoletti
Antonio
A
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004279:DNA, Viral / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000737:chemistry; D006801:Humans; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000097:blood; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
D001323:Autoantibodies; D016207:Cytokines; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I; D007075:Immunoglobulin M; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell