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J Virol. 2010 May;84(9):4461-8. doi: 10.1128/JVI.02438-09. Epub 2010 Feb 10.

Virus-specific CD8+ T-cell responses better define HIV disease progression than HLA genotype.

Author information

1
Vaccine and Infectious Disease Institute, Statistical Center for HIV Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Abstract

HLA alleles B57/58, B27, and B35 have the strongest genetic associations with HIV-1 disease progression. The mechanisms of these relationships may be host control of HIV-1 infection via CD8(+) T-cell responses. We examined these immune responses in subjects from the Seattle Primary Infection Cohort with these alleles. CD8(+) T-cell responses to conserved HIV epitopes within B57/58 alleles (TW10 and KF11) and B27 alleles (KK10 and FY10) delayed declines in CD4(+) T-cell counts (4 to 8 times longer), while responses to variable epitopes presented by B35 alleles (DL9 and IL9) resulted in more rapid progression. The plasma viral load was higher in B57/58(+) and B27(+) subjects lacking the conserved B57/58- and B27-restricted responses. The presence of certain B57/58-, B27-, and B35-restricted HIV-specific CD8(+) T-cell responses after primary HIV-1 infection better defined disease progression than the HLA genotype alone, suggesting that it is the HIV-specific CD8(+) T cells and not the presence of a particular HLA allele that determine disease progression. Further, the most effective host CD8(+) T-cell responses to HIV-1 were prevalent within an HLA allele, represented a high total allele fraction of the host CD8(+) T-cell response, and targeted conserved regions of HIV-1. These data suggest that vaccine immunogens should contain only conserved regions of HIV-1.

PMID:
20147397
PMCID:
PMC2863751
DOI:
10.1128/JVI.02438-09
[Indexed for MEDLINE]
Free PMC Article

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