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KMID : 0617319950050010076
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Journal of Pharmacetical Sceiences Ewha Womans University
1995 Volume.5 No. 1 p.76 ~ p.83
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Analysis of HLA-A2-restricted Epitope Peptides of Hepatitis B Virus Proteins
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이희구/Lee, Hee Gu
임종석/김승목/이기영/김희수/김승호/권태종/Lim, Jong-seak/Kim, Seungmoak/Lee, Ki-Young/Kim, Hee-Sue/Kim, Seung-Ho/Kwon, Tae-Jong
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Abstract
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The cytotoxic T lymphocyte (CTL) are an important component in host defense mechanism against viral infection. They can recongnize virus-derived peptides presented by the Class I MHC molecule at the cell surface of the infected cells. On searching for effective CTL epitopes of hepatitis B virus(HBV), we synthesized a distinct set of 9-10 mer peptide containing amino acid sequence of hepatitis B virus surface protein that are selected on the basis of a computer modeling and the previously described HLA-A2 specific motifs.Binding assay of the synthetic peptides to HLA-A2 molecules using human antigen processing defectant T2 cells showed that 3 out of 4 synthetic peptides enhanced the expression of HLA-A2 molecule on T2 cell surface.Two anchor positions, namely P2 and P9(or P10) appeared to play a decisive role for binding.Structural. characteristics of the peptides addressed by molecular dynamics simulation was analysed and compared.These peptides also partially triggered CTL isolated from human peripheral blood mononuclear cells of HBV positive patients, and the response was peptide-spcific.These results showed that negatively-charged amino acid residue at P2 hampered binding affinity of the peptides to HLA-A2 molecules, and that binding affinity of the peptides are not always reflected by their immunogenicity among natural T cell repertoire.
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KEYWORD
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