Hierarchical targeting of subtype C human immunodeficiency virus type 1 proteins by CD8+ T cells: correlation with viral load.
An understanding of the relationship between the breadth and magnitude of T-cell epitope responses and viral loads is important for the design of effective vaccines. For this study, we screened a cohort of 46 subtype C human immunodeficiency virus type 1 (HIV-1)-infected individuals for T-cell responses against a panel of peptides corresponding to the complete subtype C genome. We used a gamma interferon ELISPOT assay to explore the hypothesis that patterns of T-cell responses across the expressed HIV-1 genome correlate with viral control. The estimated median time from seroconversion to response for the cohort was 13 months, and the order of cumulative T-cell responses against HIV proteins was as follows: Nef > Gag > Pol > Env > Vif > Rev > Vpr > Tat > Vpu. Nef was the most intensely targeted protein, with 97.5% of the epitopes being clustered within 119 amino acids, constituting almost one-third of the responses across the expressed genome. The second most targeted region was p24, comprising 17% of the responses. There was no correlation between viral load and the breadth of responses, but there was a weak positive correlation (r = 0.297; P = 0.034) between viral load and the total magnitude of responses, implying that the magnitude of T-cell recognition did not contribute to viral control. When hierarchical patterns of recognition were correlated with the viral load, preferential targeting of Gag was significantly (r = 0.445; P = 0.0025) associated with viral control. These data suggest that preferential targeting of Gag epitopes, rather than the breadth or magnitude of the response across the genome, may be an important marker of immune efficacy. These data have significance for the design of vaccines and for interpretation of vaccine-induced responses.
Masemola
Agatha
A
National Institute for Communicable Diseases, Johannesburg, South Africa.
Mashishi
Tumelo
T
Khoury
Greg
G
Mohube
Phineas
P
Mokgotho
Pauline
P
Vardas
Efthyia
E
Colvin
Mark
M
Zijenah
Lynn
L
Katzenstein
David
D
Musonda
Rosemary
R
Allen
Susan
S
Kumwenda
Newton
N
Taha
Taha
T
Gray
Glenda
G
McIntyre
James
J
Karim
Salim Abdool
SA
Sheppard
Haynes W
HW
Gray
Clive M
CM
D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000821:virology
D000939:Epitopes; D015488:HIV Antigens