Definition of human immunodeficiency virus type 1 gp120 and gp41 cytotoxic T-lymphocyte epitopes and their restricting major histocompatibility complex class I alleles in simian-human immunodeficiency virus-infected rhesus monkeys.
With the development of chimeric simian-human immunodeficiency virus (SHIV)-infected macaques as a model for assessing novel human immunodeficiency virus type I (HIV-1) envelope glycoprotein (Env)-based vaccine strategies for preventing HIV-1 infection in man, it will be important to determine HIV-1 Env-specific cytotoxic T-lymphocyte (CTL) responses in vaccinated and virus-infected monkeys. To facilitate performing such CTL studies, we have defined two HIV-1 Env CTL epitopes in SHIV-infected rhesus monkeys and characterized the major histocompatibility complex (MHC) class I alleles that bind these Env peptide fragments and present them to CTL. A 9-amino-acid (aa) fragment of HIV-1 gp4l (p6B, aa 553 to 561) is presented to CD8+ CTLs of SHIV-infected animals by the rhesus monkey HLA-B homolog molecule Mamu-B*12. An 8-aa HIV-1 gpl.20 peptide (p9CD, aa 117 to 124) represents a CTL epitope in rhesus monkeys restricted by the HLA-A homolog MHC allele Mamu-A*08. This gp120 CTL epitope is fully conserved in all simian immunodeficiency virus, HIV-1, and HIV-2 isolates that have been sequenced to date and exhibits functional cross-reactivity. Screening of 14 unselected rhesus monkeys for expression of the two novel MHC class I alleles revealed the presence of each of the alleles in more than 40% of the animals. The characterization of the two HIV-1 Env CTL epitopes and their restricting MHC class I alleles will provide a basis for studying vaccine- and virus-elicited cytotoxic effector cell responses in rhesus monkeys.
Voss
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Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Letvin
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D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004274:DNA, Recombinant; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D000956:Antigens, Viral; D004274:DNA, Recombinant; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D015395:Histocompatibility Antigens Class I