title: Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection.
abstract: 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.
authors: Institute of Hepatology, University College London, London WC1 E6HX, United Kingdom.
authors: Stephanie
authors: S
authors: Reignat
authors: George J M
authors: GJ
authors: Webster
authors: David
authors: D
authors: Brown
authors: Graham S
authors: GS
authors: Ogg
authors: Abigail
authors: A
authors: King
authors: Suranjith L
authors: SL
authors: Seneviratne
authors: Geoff
authors: G
authors: Dusheiko
authors: Roger
authors: R
authors: Williams
authors: Mala K
authors: MK
authors: Maini
authors: Antonio
authors: A
authors: Bertoletti
mesh_terms: 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
chemical_list: 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