title: Use of major histocompatibility complex class I/peptide/beta2M tetramers to quantitate CD8(+) cytotoxic T lymphocytes specific for dominant and nondominant viral epitopes in simian-human immunodeficiency virus-infected rhesus monkeys.
abstract: To evaluate the impact of the diversity of antigen recognition by T lymphocytes on disease pathogenesis, we must be able to identify and analyze simultaneously cytotoxic T-lymphocyte (CTL) responses specific for multiple viral epitopes. Many of the studies of the role of CD8(+) CTLs in AIDS pathogenesis have been done with simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys. These studies have frequently made use of the well-defined SIV Gag CTL epitope p11C,C-M presented to CTL by the HLA-A homologue molecule Mamu-A*01. In the present study we identified and fine mapped two novel Mamu-A*01-restricted CTL epitopes: the SIVmac Pol-derived epitope p68A (STPPLVRLV) and the human immunodeficiency virus type 1 (HIV-1) Env-derived p41A epitope (YAPPISGQI). The frequency of CD8(+) CTLs specific for the p11C,C-M, p68A, and p41A epitopes was quantitated in the same animals with a panel of tetrameric Mamu-A*01/peptide/beta2m complexes. All SHIV-infected Mamu-A*01(+) rhesus monkeys tested had a high frequency of SIVmac Gag-specific CTLs to the p11C,C-M epitope. In contrast, only a fraction of the monkeys tested had detectable CTLs specific for the SIVmac Pol p68A and HIV-1 Env p41A epitopes, and these responses were detected at very low frequencies. Thus, the p11C,C-M-specific CD8(+) CTL response is dominant and the p41A- and p68A-specific CD8(+) CTL responses are nondominant. These results indicate that CD8(+) CTL responses to dominant CTL epitopes can be readily quantitated with the tetramer technology; however, CD8(+) CTL responses to nondominant epitopes, due to the low frequency of these epitope-specific cells, may be difficult to detect and quantitate by this approach.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. michael_egan@caregroup.harvard.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Egan
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: G
authors.initials: G
authors.lastname: Voss
authors.forename: J E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: W A
authors.initials: WA
authors.lastname: Charini
authors.forename: C I
authors.initials: CI
authors.lastname: Lord
authors.forename: M A
authors.initials: MA
authors.lastname: Forman
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015684:Gene Products, pol / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015684:Gene Products, pol; D015700:HIV Envelope Protein gp41; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D010455:Peptides; D001613:beta 2-Microglobulin