BACKGROUND & AIMS: Different amino acid sequences of hepatitis B virus surface antigen (HBsAg) are involved in the activation of CD4+ lymphocytes needed to induce an optimal antiviral function. The aim of this study was to characterize the CD4-mediated response to immunodominant HBsAg epitopes in hepatitis B virus (HBV) vaccine recipients by defining minimal sequences recognized by T cells, cytokine profiles, and HLA restriction of peptide recognition. METHODS: T-lymphocyte lines and clones specific for HBsAg were isolated from the peripheral blood of subjects immunized with recombinant HBsAg and stimulated in vitro with synthetic peptides spanning the whole HBsAg sequence. RESULTS: Four immunodominant epitopes (sequences 21-40, 136-155, 156-175, and 211-226) were identified. Using panels of truncated peptides of different length, sequences 21-28, 165-172, and 215-223 were shown to correspond to the minimal epitopes recognized by T cells. The antigen-specific T-lymphocyte proliferation was HLA class II restricted, and each peptide could be presented in association with different HLA class II determinants. Th0/Th2 cytokine patterns were induced on peptide stimulation. CONCLUSIONS: These results indicate the presence of at least four immunodominant epitopes within HBsAg that represent potential candidates for the design of anti-HBV synthetic vaccines.
BACKGROUND & AIMS: Different amino acid sequences of hepatitis B virus surface antigen (HBsAg) are involved in the activation of CD4+ lymphocytes needed to induce an optimal antiviral function. The aim of this study was to characterize the CD4-mediated response to immunodominant HBsAg epitopes in hepatitis B virus (HBV) vaccine recipients by defining minimal sequences recognized by T cells, cytokine profiles, and HLA restriction of peptide recognition. METHODS: T-lymphocyte lines and clones specific for HBsAg were isolated from the peripheral blood of subjects immunized with recombinant HBsAg and stimulated in vitro with synthetic peptides spanning the whole HBsAg sequence. RESULTS: Four immunodominant epitopes (sequences 21-40, 136-155, 156-175, and 211-226) were identified. Using panels of truncated peptides of different length, sequences 21-28, 165-172, and 215-223 were shown to correspond to the minimal epitopes recognized by T cells. The antigen-specific T-lymphocyte proliferation was HLA class II restricted, and each peptide could be presented in association with different HLA class II determinants. Th0/Th2 cytokine patterns were induced on peptide stimulation. CONCLUSIONS: These results indicate the presence of at least four immunodominant epitopes within HBsAg that represent potential candidates for the design of anti-HBV synthetic vaccines.
Authors: Philip J Norris; Howell F Moffett; Christian Brander; Todd M Allen; Kristin M O'Sullivan; Lisa A Cosimi; Daniel E Kaufmann; Bruce D Walker; Eric S Rosenberg Journal: AIDS Res Hum Retroviruses Date: 2004-03 Impact factor: 2.205
Authors: Julia Schwaiger; Judith H Aberle; Karin Stiasny; Bernhard Knapp; Wolfgang Schreiner; Ingrid Fae; Gottfried Fischer; Ondrej Scheinost; Vaclav Chmelik; Franz X Heinz Journal: J Virol Date: 2014-04-30 Impact factor: 5.103
Authors: Patricia Aguilar; Edith Renoult; Loraine Jarrosson; Marie Nathalie Kolopp-Sarda; Christine Prin Mathieu; Gilbert C Faure; Michele Kessler; Marie C Bene; Chantal Kohler; Anne Kennel De March Journal: Clin Diagn Lab Immunol Date: 2003-11