Human Immunodeficiency Virus Type 1 Nef Epitopes Recognized in HLA-A2 Transgenic Mice in Response to DNA and Peptide Immunization
Identifieur interne : 003739 ( Main/Exploration ); précédent : 003738; suivant : 003740Human Immunodeficiency Virus Type 1 Nef Epitopes Recognized in HLA-A2 Transgenic Mice in Response to DNA and Peptide Immunization
Auteurs : Johan K. Sandberg [Suède] ; Ann-Charlotte Leandersson [Suède] ; Claudia Devito [Suède] ; Birgit Kohleisen [Allemagne] ; Volker Erfle [Allemagne] ; Adnane Achour [Suède] ; Michael Levi [Suède] ; Stefan Schwartz [Suède] ; Klas K Rre [Suède] ; Britta Wahren [Suède] ; Jorma Hinkula [Suède]Source :
- Virology [ 0042-6822 ] ; 2000.
English descriptors
- Teeft :
- Active antiretroviral therapy, Assay, Binding capacity, Binding peptides, Cell surface, Coefficient tables, Complete medium, Ctls, Cytotoxic, Cytotoxic responses, Effector cells, Epitope, Good binders, Helper cell proliferation, High frequency, Human immunodeficiency virus, Human immunodeficiency virus type, Immune responses, Immune splenocytes, Immunization, Immunodeficiency, Immunodeficiency virus type, Immunol, Karolinska institutet, Kenneth parker, Lymphocyte, Lymphocyte responses, Major histocompatibility, Peptide, Peptide fragments, Peptide immunization, Proliferative responses, Protein sequence, Putative binding peptides, Search algorithm, Search engine, Several epitopes, Several peptides, Simian immunodeficiency virus, Specific ctls, Specific peptide, Spleen cells, Stabilization assay, Synthetic peptides, Target cells, Tissue culture medium, Transgenic, Transgenic mice, Tumor biology center, Vaccine, Vaccine development, Viral, Viral peptides, Virol.
Abstract
Abstract: We investigated the immune response against a human immunodeficiency virus type 1 (HIV-1) nef DNA sequence administered epidermally in mice transgenic for the human major histocompatibility complex (MHC) class I molecule HLA-A201. Ten potential HLA-A2 binding 9-mer Nef peptides were identified by a computer-based search algorithm. By a cell surface MHC class I stabilization assay, four peptides were scored as good binders, whereas two peptides bound weakly to HLA-A2. After DNA immunization, cytotoxic T lymphocyte (CTL) responses were predominantly directed against the Nef 44-52, 81-89, and 85-93 peptides. Interestingly, the 44-52 epitope resides outside the regions of Nef where previously described CTL epitopes are clustered. Dominance among Nef-derived peptides did not strictly correlate with HLA-A2 binding, in that only one of the high-affinity binding peptides was targeted in the CTL response. The 44-52, 85-93, and 139-147 peptides also generated specific CTLs in response to peptide immunization. T helper cell proliferation was detected after stimulation with 20-mer peptides in vitro. Three Nef regions (16-35, 106-125, and 166-185) dominated the T helper cell proliferation. The implications of these results for the development of DNA-based vaccines against HIV is discussed.
Url:
DOI: 10.1006/viro.2000.0360
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">Abstract: We investigated the immune response against a human immunodeficiency virus type 1 (HIV-1) nef DNA sequence administered epidermally in mice transgenic for the human major histocompatibility complex (MHC) class I molecule HLA-A201. Ten potential HLA-A2 binding 9-mer Nef peptides were identified by a computer-based search algorithm. By a cell surface MHC class I stabilization assay, four peptides were scored as good binders, whereas two peptides bound weakly to HLA-A2. After DNA immunization, cytotoxic T lymphocyte (CTL) responses were predominantly directed against the Nef 44-52, 81-89, and 85-93 peptides. Interestingly, the 44-52 epitope resides outside the regions of Nef where previously described CTL epitopes are clustered. Dominance among Nef-derived peptides did not strictly correlate with HLA-A2 binding, in that only one of the high-affinity binding peptides was targeted in the CTL response. The 44-52, 85-93, and 139-147 peptides also generated specific CTLs in response to peptide immunization. T helper cell proliferation was detected after stimulation with 20-mer peptides in vitro. Three Nef regions (16-35, 106-125, and 166-185) dominated the T helper cell proliferation. The implications of these results for the development of DNA-based vaccines against HIV is discussed.</div>
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