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.
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.
Streeck
Hendrik
H
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Lichterfeld
Mathias
M
Alter
Galit
G
Meier
Angela
A
Teigen
Nickolas
N
Yassine-Diab
Bader
B
Sidhu
Harlyn K
HK
Little
Susan
S
Kelleher
Anthony
A
Routy
Jean-Pierre
JP
Rosenberg
Eric S
ES
Sekaly
Rafick-Pierre
RP
Walker
Bruce D
BD
Altfeld
Marcus
M
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
D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I