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Your search keyword '"Shao Chong Zhang"' showing total 2 results
Start Over Author "Shao Chong Zhang" Journal journal of clinical investigation
2 results on '"Shao Chong Zhang"'

1. Variable HIV peptide stability in human cytosol is critical to epitope presentation and immune escape

Author

Mei Zhang, David Heckerman, Sylvie Le Gall, Estibaliz Lazaro, Carl M. Kadie, Pamela Stamegna, Sergio A. Martinez, Pauline Gourdain, Nicole Y. Lai, and Shao Chong Zhang

Subjects
HIV Antigens, T cell, Amino Acid Motifs, Molecular Sequence Data, Antigen presentation, HIV Core Protein p24, T-Cell Antigen Receptor Specificity, Peptide, HLA-A3 Antigen, In Vitro Techniques, Biology, Histone Deacetylase 6, gag Gene Products, Human Immunodeficiency Virus, Histone Deacetylases, Epitope, Epitopes, Cytosol, Consensus Sequence, Consensus sequence, medicine, Humans, Amino Acid Sequence, HSP90 Heat-Shock Proteins, Peptide sequence, AIDS Vaccines, chemistry.chemical_classification, Antigen Presentation, HLA-A Antigens, Linear epitope, Protein Stability, Computational Biology, General Medicine, Virology, HIV Reverse Transcriptase, Peptide Fragments, CTL, medicine.anatomical_structure, chemistry, HLA-B Antigens, HIV-1, Algorithms, Research Article, Half-Life, T-Lymphocytes, Cytotoxic
Abstract

Induction of virus-specific CD8⁺ T cell responses is critical for the success of vaccines against chronic viral infections. Despite the large number of potential MHC-I-restricted epitopes located in viral proteins, MHC-I-restricted epitope generation is inefficient, and factors defining the production and presentation of MHC-I-restricted viral epitopes are poorly understood. Here, we have demonstrated that the half-lives of HIV-derived peptides in cytosol from primary human cells were highly variable and sequence dependent, and significantly affected the efficiency of cell recognition by CD8⁺ T cells. Furthermore, multiple clinical isolates of HLA-associated HIV epitope variants displayed reduced half-lives relative to consensus sequence. This decreased cytosolic peptide stability diminished epitope presentation and CTL recognition, illustrating a mechanism of immune escape. Chaperone complexes including Hsp90 and histone deacetylase HDAC6 enhanced peptide stability by transient protection from peptidase degradation. Based on empirical results with 166 peptides, we developed a computational approach utilizing a sequence-based algorithm to estimate the cytosolic stability of antigenic peptides. Our results identify sequence motifs able to alter the amount of peptide available for loading onto MHC-I, suggesting potential new strategies to modulate epitope production from vaccine immunogens.

Published
2011
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2. Variable HIV peptide stability in human cytosol is critical to epitope presentation and immune escape.

Author

Lazaro, Estibaliz, Kadie, Carl, Stamegna, Pamela, Shao Chong Zhang, Gourdain, Pauline, Lai, Nicole Y., Mei Zhang, Martinez, Sergio A., Heckerman, David, Le Gall, Sylvie, Zhang, Shao Chong, and Zhang, Mei

Subjects
*PEPTIDES, *CYTOSOL, *EPITOPES, *MOLECULAR chaperones, *HISTONE deacetylase, *VIRUS diseases, *LABORATORY mice, *AIDS vaccines, *ALGORITHMS, *AMINO acids, *ANTIGENS, *BIOCHEMISTRY, *CELLULAR immunity, *COMPARATIVE studies, *DOCUMENTATION, *HIV, *HYDROLASES, *IMMUNITY, *PHENOMENOLOGY, *RESEARCH methodology, *MEDICAL cooperation, *MOLECULAR structure, *PROTEINS, *RESEARCH, *RESEARCH funding, *T cells, *TIME, *VIRAL antigens, *HLA-B27 antigen, *BIOINFORMATICS, *EVALUATION research, *IN vitro studies
Abstract

Induction of virus-specific CD8⁺ T cell responses is critical for the success of vaccines against chronic viral infections. Despite the large number of potential MHC-I-restricted epitopes located in viral proteins, MHC-I-restricted epitope generation is inefficient, and factors defining the production and presentation of MHC-I-restricted viral epitopes are poorly understood. Here, we have demonstrated that the half-lives of HIV-derived peptides in cytosol from primary human cells were highly variable and sequence dependent, and significantly affected the efficiency of cell recognition by CD8⁺ T cells. Furthermore, multiple clinical isolates of HLA-associated HIV epitope variants displayed reduced half-lives relative to consensus sequence. This decreased cytosolic peptide stability diminished epitope presentation and CTL recognition, illustrating a mechanism of immune escape. Chaperone complexes including Hsp90 and histone deacetylase HDAC6 enhanced peptide stability by transient protection from peptidase degradation. Based on empirical results with 166 peptides, we developed a computational approach utilizing a sequence-based algorithm to estimate the cytosolic stability of antigenic peptides. Our results identify sequence motifs able to alter the amount of peptide available for loading onto MHC-I, suggesting potential new strategies to modulate epitope production from vaccine immunogens. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

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