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

Harvard University, Cambridge, Massachusetts, United States
Journal of Virology (Impact Factor: 4.44). 07/2007; 81(14):7725-31. DOI: 10.1128/JVI.00708-07
Source: PubMed


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.

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Available from: Jean-Pierre Routy, Jan 20, 2014
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    • "CTLs are activated by binding to antigenic peptides presented by HLA, initiating the immune response. Many studies report the effect of HLA polymorphisms on the progression of AIDS [112, 113]. Many HLA alleles have been correlated with rapid disease progression, as HLA-A24, -A29, -B35, -C4, -DR1, and -DR3, whereas patients carrying HLA-B14, -B27, -B57, -C8, or -DR6 appear to develop AIDS more slowly [114, 115]. "
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    • "Although we cannot be sure that the presence of heterologous neutralizing antibodies would have been efficient in preventing superinfection if they had been present, it seems likely that the risk of superinfection was increased by the lack of such antibodies. The control of HIV-1 in HLA-B57 patients has been attributed to an early and immunodominant CTL response targeting a highly conserved Gag epitope, TW10 (Streeck et al., 2007). In patient 4050, dominant responses were observed at T1 and one year after superinfection and were directed mainly toward two epitopes in Gag, IW9 and KF11, but more moderately toward TW10. "
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