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Immunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents

Bansal, Anjua; Yue, Linga; Conway, Joana; Yusim, Karinae; Tang, Jianminga,b; Kappes, Johna; Kaslow, Richard Aa,c; Wilson, Craig Ma,d; Goepfert, Paul Aa,b

doi: 10.1097/QAD.0b013e3282f13823
Basic Science

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-γ ELISpot and ICS assays.

Results: In an interferon-γ 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.

From the aDepartment of Medicine, USA

bDepartment of Microbiology, USA

cDepartment of Epidemiology, USA

dDepartment of Pediatrics, University of Alabama at Birmingham, Alabama, USA

eLos Alamos National Laboratory, Los Alamos, NM 87545 and the Adolescent Trials Network for HIV/AIDS intervention.

Received 11 May, 2007

Revised 10 July, 2007

Accepted 16 August, 2007

Correspondence to Paul A. Goepfert, Department of Medicine, University of Alabama at Birmingham, 908, 20th Street South, CCB 330, Birmingham, AL 35294, USA. Tel: +1 205 975 5667; fax: +1 205 975 5718; e-mail: paulg@uab.edu

© 2007 Lippincott Williams & Wilkins, Inc.