Effects of lamivudine on the hepatitis B virus specific CD8+ cytotoxic T lymphocyte responses via peptide-MHC tetrameric complexes assay

2001 ◽  
Vol 8 (3-5) ◽  
pp. 179-185 ◽  
Author(s):  
Tzong-Hsien Lee ◽  
Yen-Ling Chuang ◽  
Sun-Lung Tsai ◽  
Yun-Fan Liaw
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
B Virus ◽  
Lymphocyte Responses

scholarly journals Efficient Generation of a Hepatitis B Virus Cytotoxic T Lymphocyte Epitope Requires the Structural Features of Immunoproteasomes

2000 ◽  
Vol 191 (3) ◽  
pp. 503-514 ◽  
Author(s):  
Alice J.A.M. Sijts ◽  
Thomas Ruppert ◽  
Barbara Rehermann ◽  
Marion Schmidt ◽  
Ulrich Koszinowski ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Structural Features ◽  
Core Antigen ◽  
Ctl Epitope ◽  
Cleavage Specificity ◽  
B Virus ◽  
Ifn Γ

Interferon (IFN)-γ–induced cells express the proteasome subunits low molecular weight protein (LMP)2, LMP7, and MECL-1 (multicatalytic endopeptidase complex–like 1), leading to the formation of immunoproteasomes. Although these subunits are thought to optimize MHC class I antigen processing, the extent of their role and the mechanistic aspects involved remain unclear. Herein, we study the proteolytic generation of an human histocompatibility leukocyte antigen (HLA)-Aw68–restricted hepatitis B virus core antigen (HBcAg) cytotoxic T lymphocyte (CTL) epitope that is recognized by peripheral blood lymphocytes from patients with acute self-limited but not chronic hepatitis B virus (HBV). Immunological data suggest that IFN-γ–induced rather than uninduced HeLa cells process and present the HBV CTL epitope upon infection with HBcAg-expressing vaccinia viruses. Analyses of 20S proteasome digests of synthetic polypeptides covering the antigenic HBcAg peptide demonstrate that only immunoproteasomes efficiently perform the cleavages needed for the liberation of this HBV CTL epitope. Although the concerted presence of the three immunosubunits appears essential, we find that both catalytically active LMP7 and inactive LMP7 T1A support CTL epitope generation. We conclude that LMP7 influences the structural features of 20S proteasomes, thereby enhancing the activity of the LMP2 and MECL-1 catalytic sites, which provide cleavage specificity. Thus, LMP7 incorporation is of greater functional importance for the generation of an HBV CTL epitope than cleavage specificity.

Is antigenic variability a strategy adopted by hepatitis B virus to escape cytotoxic T-lymphocyte surveillance?

1996 ◽  
Vol 7 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Carlo Ferrari ◽  
Antonio Bertoletti ◽  
Franco Fiaccadori ◽  
Francis V. Chisari*
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigenic Variability ◽  
B Virus

scholarly journals Cytotoxic T-Lymphocyte Antigen 4 Gene and Recovery from Hepatitis B Virus Infection

2004 ◽  
Vol 78 (20) ◽  
pp. 11258-11262 ◽  
Author(s):  
Chloe L. Thio ◽  
Timothy L. Mosbruger ◽  
Richard A. Kaslow ◽  
Christopher L. Karp ◽  
Steffanie A. Strathdee ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Lymphocyte ◽  
Cell Response ◽  
Cytotoxic T Lymphocyte ◽  
Viral Persistence ◽  
T Cell Response ◽  
Hbv Infection ◽  
B Virus

ABSTRACT Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory T-cell receptor expressed by activated and regulatory T cells. We hypothesized that single-nucleotide polymorphisms (SNPs) in the gene encoding CTLA-4 may affect the vigor of the T-cell response to hepatitis B virus (HBV) infection, thus influencing viral persistence. To test this hypothesis, we genotyped six CTLA4 SNPs, from which all frequent haplotypes can be determined, using a large, matched panel of subjects with known HBV outcomes. Haplotypes with these SNPs were constructed for each subject using PHASE software. The haplotype distribution differed between those with viral persistence and those with clearance. Two haplotypes were associated with clearance of HBV infection, which was most likely due to associations with the SNPs −1722C (odds ratio [OR] = 0.60, P = 0.06) and +49G (OR = 0.73, P = 0.02). The wild-type haplotype, which contains an SNP leading to a decreased T-cell response (+6230A), was associated with viral persistence (OR = 1.32, P = 0.04). These data suggest that CTLA4 influences recovery from HBV infection, which is consistent with the emerging role of T regulatory cells in the pathogenesis of disease.

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