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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 : 003740

Human 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 :

RBID : ISTEX:1E1CA17AAFB82B252BD7281C75CDE2EAE3FE7D63

English descriptors

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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<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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