Journal
AIDS
Volume 21, Issue 18, Pages 2387-2397Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e3282f13823
Keywords
adolescents; CD8 T-cells; Gag; HIV-1; HLA-class I; Nef
Categories
Funding
- NCRR NIH HHS [M01 RR000240, M01 RR013297, M01 RR005096] Funding Source: Medline
- NIAID NIH HHS [R01 AI064060-03, AI41951, R01 AI041951, R21 AI073103, AI49126, R21 AI073103-01A1, R01 AI041951-08, R01 AI084772, R21 AI049126, R01 AI064060, R01 AI049126] Funding Source: Medline
- NICHD NIH HHS [U01 HD40533, U01 HD040533, U01 HD040474, U01 HD32830] Funding Source: Medline
- PHS HHS [A1064060, A1073103-01] Funding Source: Medline
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Background: Differential protein targeting by HIV-specific CD8 T cells is associated with disparate plasma viral loads; however, it is unclear if the quality of these responses differs depending upon the specificity of the targeted epitopes. Methods: We examined HIV-specific CD8 T-cell responses in HIV-infected adolescents carrying either an HLA class I allele associated with a favorable prognosis (HLA-B*57) or an allele associated with usual disease progression (HLA-B*35 or HLA-B*53) using interferon-gamma ELISpot and ICS assays. Results: In an interferon-gamma ELISpot assay, p24 was the dominant protein targeted by B*57 carriers while responses to Nef dominated in B*35 or B*53 positive carriers. This differential protein targeting did not change during 4 years of follow-up. In these chronically infected adolescents, there were no significant differences in the quality of the immunodominant T-cell responses between the B*57 and B*35/B*53 carriers as measured by peptide avidity, degranulation, and immune memory markers. There was a trend towards higher expression of interleukin-2 from B*57-KF11 restricted CD8 T cells although this difference was not significant. Nevertheless both B*57 and B*35/53 restricted responses were relatively potent as reflected by the propensity of CD8 T cells to escape in p24 and Nef, respectively. Conclusions: Differential protein targeting rather than the quality of T-cell responses appears to be a major distinguishing feature of HIV-specific CD8 T cells induced in B*57 carriers. These data suggest that viral fitness costs associated with CD8 T-cell pressure is an important factor determining differences in the viral load among HIV-infected patients. (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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