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- Title
Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents.
- Authors
Sharp, Elizabeth R.; Willberg, Christian B.; Kuebler, Peter J.; Abadi, Jacob; Fennelly, Glenn J.; Dobroszycki, Joanna; Wiznia, Andrew A.; Rosenberg, Michael G.; Nixon, Douglas F.
- Abstract
Background: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. Methodology/Principal Findings: In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%$25 were categorized as having no immune suppression (NS), and those with CD4%#15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLAB* 57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of nai&vuml;e CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. Conclusions/Significance: Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1- Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions.
- Subjects
UNITED States; T cells; CD8 antigen; HIV; IMMUNOSUPPRESSION; DISEASE progression; JUVENILE diseases; ANTIRETROVIRAL agents
- Publication
PLoS ONE, 2011, Vol 6, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0021135