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Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection

Reignat, S; Webster, GJM; Brown, D; Ogg, GS; King, A; Seneviratne, SL; ... Bertoletti, A; + view all (2002) Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection. J EXP MED , 195 (9) 1089 - 1101. 10.1084/jem.20011723.

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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 4 CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.

Type:Article
Title:Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection
DOI:10.1084/jem.20011723
Keywords:cytotoxic T lymphocytes, chronic hepatitis B, viral diseases, immune tolerance, viral T antigen, LYMPHOCYTIC CHORIOMENINGITIS VIRUS, ACTIVATED T-CELLS, EFFECTOR FUNCTION, FUNCTIONAL AVIDITY, TRANSGENIC MICE, SURFACE-ANTIGEN, IMMUNE EVASION, CUTTING EDGE, TCR AVIDITY, IN-VITRO
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Infection and Immunity (Division of)

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