Virus-specific CD8+ T-cell responses better define HIV disease progression than HLA genotype.
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.
Vaccine and Infectious Disease Institute, Statistical Center for HIV Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Warren L
WL
Dinges
Julia
J
Richardt
David
D
Friedrich
Emilie
E
Jalbert
Yi
Y
Liu
Claire E
CE
Stevens
Janine
J
Maenza
Ann C
AC
Collier
Daniel E
DE
Geraghty
Jeremy
J
Smith
Zoe
Z
Moodie
James I
JI
Mullins
M Juliana
MJ
McElrath
Helen
H
Horton
D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D019562:Viral Load
D006680:HLA Antigens