title: Consistent patterns in the development and immunodominance of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses following acute HIV-1 infection.
abstract: Human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses generated during acute infection play a critical role in the initial control of viremia. However, little is known about the viral T-cell epitopes targeted during acute infection or about their hierarchy in appearance and relative immunodominance over time. In this study, HIV-1-specific CD8+ T-cell responses in 18 acutely infected individuals expressing HLA-A3 and/or -B7 were characterized. Detailed analysis of CD8 responses in one such person who underwent treatment of acute infection followed by reexposure to HIV-1 through supervised treatment interruptions (STI) revealed recognition of only two cytotoxic T-lymphocyte (CTL) epitopes during symptomatic acute infection. HIV-1-specific CD8+ T-cell responses broadened significantly during subsequent exposure to the virus, ultimately targeting 27 distinct CTL epitopes, including 15 different CTL epitopes restricted by a single HLA class I allele (HLA-A3). The same few peptides were consistently targeted in an additional 17 persons expressing HLA-A3 and/or -B7 during acute infection. These studies demonstrate a consistent pattern in the development of epitope-specific responses restricted by a single HLA allele during acute HIV-1 infection, as well as persistence of the initial pattern of immunodominance during subsequent STI. In addition, they demonstrate that HIV-1-specific CD8+ T-cell responses can ultimately target a previously unexpected and unprecedented number of epitopes in a single infected individual, even though these are not detectable during the initial exposure to virus. These studies have important implications for vaccine design and evaluation.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: William R
authors.initials: WR
authors.lastname: Rodriguez
authors.forename: Paul K
authors.initials: PK
authors.lastname: Lee
authors.forename: Cecily A
authors.initials: CA
authors.lastname: Fitzpatrick
authors.forename: Mary N
authors.initials: MN
authors.lastname: Johnston
authors.forename: Daryld
authors.initials: D
authors.lastname: Strick
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D015791:HLA-A3 Antigen / Q000378:metabolism; D015793:HLA-B7 Antigen / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D014764:Viral Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology
chemical_list: D015791:HLA-A3 Antigen; D015793:HLA-B7 Antigen; D016056:Immunodominant Epitopes; D010455:Peptides; D014764:Viral Proteins