title: Recognition of a defined region within p24 gag by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I alleles.
abstract: Human immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8(+) T-cell responses in individuals expressing protective HLA class I alleles. Here we compared HIV-1-specific T-cell responses between subjects expressing the protective allele HLA-B27 or -B57 and subjects expressing nonprotective HLA alleles using a cohort of over 290 subjects identified during primary HIV-1 infection. CD8(+) T cells of individuals expressing HLA-B27 or -B57 targeted a defined region within HIV-1 p24 Gag (amino acids 240 to 272) early in infection, and responses against this region contributed over 35% to the total HIV-1-specific T-cell responses in these individuals. In contrast, this region was rarely recognized in individuals expressing HLA-B35, an HLA allele associated with rapid disease progression, or in subjects expressing neither HLA-B57/B27 nor HLA-B35 (P < 0.0001). The identification of this highly conserved region in p24 Gag targeted in primary infection specifically in individuals expressing HLA class I alleles associated with slower HIV-1 disease progression provides a rationale for vaccine design aimed at inducing responses to this region restricted by other, more common HLA class I alleles.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Angela
authors.initials: A
authors.lastname: Meier
authors.forename: Nickolas
authors.initials: N
authors.lastname: Teigen
authors.forename: Bader
authors.initials: B
authors.lastname: Yassine-Diab
authors.forename: Harlyn K
authors.initials: HK
authors.lastname: Sidhu
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Anthony
authors.initials: A
authors.lastname: Kelleher
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag / Q000737:chemistry / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000302:isolation & purification*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I