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

TitleImmunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents.
Publication TypePublication
Year of Publication2007
AuthorsBansal A, Yue L, Conway J, Yusim K, Tang J, Kappes J, Kaslow RA, Wilson CM, Goepfert PA
JournalAIDS
Volume21
Issue18
Pagination2387-97
Date Published2007 Nov 30
ISSN1473-5571
KeywordsAdolescent, Amino Acid Sequence, CD8-Positive T-Lymphocytes, Chronic Disease, Cross-Sectional Studies, Disease Progression, Female, Follow-Up Studies, Gene Products, gag, Genetic Predisposition to Disease, HIV Core Protein p24, HIV Infections, HIV-1, HLA Antigens, HLA-B Antigens, HLA-B35 Antigen, Humans, Immunodominant Epitopes, Interleukin-2, Molecular Sequence Data, Mutation, nef Gene Products, Human Immunodeficiency Virus, Prognosis, Viral Load
Abstract

<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>

DOI10.1097/QAD.0b013e3282f13823
Alternate JournalAIDS
PubMed ID18025875
PubMed Central IDPMC2268022
Grant ListU01 HD040533 / HD / NICHD NIH HHS / United States
U01 HD040474 / HD / NICHD NIH HHS / United States
R21 AI073103-01A1 / AI / NIAID NIH HHS / United States
R01 AI064060-03 / AI / NIAID NIH HHS / United States
AI41951 / AI / NIAID NIH HHS / United States
R01 AI041951 / AI / NIAID NIH HHS / United States
M01 RR005096 / RR / NCRR NIH HHS / United States
U01 HD32830 / HD / NICHD NIH HHS / United States
A1073103-01 / / PHS HHS / United States
R01 AI084772 / AI / NIAID NIH HHS / United States
R21 AI049126 / AI / NIAID NIH HHS / United States
R21 AI073103 / AI / NIAID NIH HHS / United States
R01 AI064060 / AI / NIAID NIH HHS / United States
A1064060 / / PHS HHS / United States
R01 AI049126 / AI / NIAID NIH HHS / United States
R01 AI041951-08 / AI / NIAID NIH HHS / United States
U01 HD40533 / HD / NICHD NIH HHS / United States
M01 RR013297 / RR / NCRR NIH HHS / United States
AI49126 / AI / NIAID NIH HHS / United States
M01 RR000240 / RR / NCRR NIH HHS / United States