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Virus-Specific CD8 + T-Cell Responses Better Define HIV Disease Progression than HLA Genotype

2010; American Society for Microbiology; Volume: 84; Issue: 9 Linguagem: Inglês

10.1128/jvi.02438-09

1098-5514

Warren L. Dinges, Julia Richardt, David Friedrich, Emilie Jalbert, Yi Liu, Claire E. Stevens, Janine Maenza, Ann C. Collier, Daniel E. Geraghty, Jeremy Smith, Zoe Moodie, James I. Mullins, M. Juliana McElrath, Helen Horton,

T-cell and B-cell Immunology

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.