title: CD8(+) lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule mamu-A*01: implications for vaccine design and testing.
abstract: It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8(+) response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8(+) epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*01(2), a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparent K(d) values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01(+) macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.
authors.affiliation: Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Allen
authors.forename: B R
authors.initials: BR
authors.lastname: Mothé
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.forename: P
authors.initials: P
authors.lastname: Jing
authors.forename: J L
authors.initials: JL
authors.lastname: Dzuris
authors.forename: M E
authors.initials: ME
authors.lastname: Liebl
authors.forename: T U
authors.initials: TU
authors.lastname: Vogel
authors.forename: D H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: M C
authors.initials: MC
authors.lastname: Wussow
authors.forename: J A
authors.initials: JA
authors.lastname: Thomson
authors.forename: J D
authors.initials: JD
authors.lastname: Altman
authors.forename: D I
authors.initials: DI
authors.lastname: Watkins
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D010455:Peptides