HIV-1 Nef is preferentially recognized by CD8 T cells in primary HIV-1 infection despite a relatively high degree of genetic diversity.
OBJECTIVE
To compare the magnitude, breadth and protein specificity of HIV-1-specific CD8 T-cell responses against the clade B consensus sequence during primary and chronic HIV-1 infection and to analyze the impact of viral diversity on the localization of detected responses.


METHODS
HIV-1-specific CD8 T-cell responses against the clade B consensus sequence in individuals with acute (n = 10), early (n = 19) and chronic (n = 10) infection were longitudinally assessed using an interferon-gamma EliSpot assay.


RESULTS
CD8 T-cell responses against clade B consensus sequences were preferentially directed against central regions of Nef during primary HIV-1 infection, despite a relatively higher degree of genetic diversity compared with other subsequently targeted regions. In subjects with acute and early infection, Nef-specific CD8 T-cell responses against the consensus Nef sequence represented 94 and 46% of the total magnitude of HIV-1-specific CD8 T-cell responses, respectively. Subjects with untreated chronic infection exhibited broadly diversified CD8 T-cell responses against more conserved viral regions, with only 17% of virus-specific T-cell responses targeting Nef. The initial immunodominance of Nef persisted in individuals with treated acute infection, but shifted rapidly to Gag, Env and Pol in subjects with continuous antigen exposure.


CONCLUSIONS
These data show that despite relatively high sequence variability, viral regions within the clade B consensus sequence of Nef are preferentially recognized during primary HIV-1 infection. Later diversification of responses to other proteins during prolonged antigen exposure provides evidence of the initial preferential immunogenicity of Nef epitopes compared to similarly conserved regions within other viral proteins.
Lichterfeld
Mathias
M
Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA.
Yu
Xu G
XG
Cohen
Daniel
D
Addo
Marylyn M
MM
Malenfant
Jessica
J
Perkins
Beth
B
Pae
Eunice
E
Johnston
Mary N
MN
Strick
Daryld
D
Allen
Todd M
TM
Rosenberg
Eric S
ES
Korber
Bette
B
Walker
Bruce D
BD
Altfeld
Marcus
M
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005814:Genes, Viral / Q000276:immunology; D015754:Genes, nef / Q000235:genetics* / Q000276:immunology; D014644:Genetic Variation / Q000276:immunology; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
D015678:Viral Structural Proteins