Recognition of a Defined Region within p24 Gag by CD8+ T Cells during Primary Human Immunodeficiency Virus Type 1 Infection in Individuals Expressing …

H Streeck, M Lichterfeld, G Alter, A Meier… - Journal of …, 2007 - Am Soc Microbiol
H Streeck, M Lichterfeld, G Alter, A Meier, N Teigen, B Yassine-Diab, HK Sidhu, S Little
Journal of virology, 2007Am Soc Microbiol
Human immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary
HIV-1 infection appear to play a critical role in determining the ultimate speed of disease
progression, but little is known about the specificity of the initial HIV-1-specific CD8+ T-cell
responses in individuals expressing protective HLA class I alleles. Here we compared HIV-1-
specific T-cell responses between subjects expressing the protective allele HLA-B27 or-B57
and subjects expressing nonprotective HLA alleles using a cohort of over 290 subjects …
Abstract
Human immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8+ T-cell responses in individuals expressing protective HLA class I alleles. Here we compared HIV-1-specific T-cell responses between subjects expressing the protective allele HLA-B27 or -B57 and subjects expressing nonprotective HLA alleles using a cohort of over 290 subjects identified during primary HIV-1 infection. CD8+ T cells of individuals expressing HLA-B27 or -B57 targeted a defined region within HIV-1 p24 Gag (amino acids 240 to 272) early in infection, and responses against this region contributed over 35% to the total HIV-1-specific T-cell responses in these individuals. In contrast, this region was rarely recognized in individuals expressing HLA-B35, an HLA allele associated with rapid disease progression, or in subjects expressing neither HLA-B57/B27 nor HLA-B35 (P < 0.0001). The identification of this highly conserved region in p24 Gag targeted in primary infection specifically in individuals expressing HLA class I alleles associated with slower HIV-1 disease progression provides a rationale for vaccine design aimed at inducing responses to this region restricted by other, more common HLA class I alleles.
American Society for Microbiology