Title | Immunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents. |
Publication Type | Publication |
Year of Publication | 2007 |
Authors | Bansal A, Yue L, Conway J, Yusim K, Tang J, Kappes J, Kaslow RA, Wilson CM, Goepfert PA |
Journal | AIDS |
Volume | 21 |
Issue | 18 |
Pagination | 2387-97 |
Date Published | 2007 Nov 30 |
ISSN | 1473-5571 |
Keywords | Adolescent, 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> |
DOI | 10.1097/QAD.0b013e3282f13823 |
Alternate Journal | AIDS |
PubMed ID | 18025875 |
PubMed Central ID | PMC2268022 |
Grant List | U01 HD040533 / HD / NICHD 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 R21 AI073103 / AI / NIAID NIH HHS / United States R01 AI049126 / AI / NIAID NIH HHS / United States M01 RR000240 / RR / NCRR NIH HHS / United States U01 HD040474 / HD / NICHD NIH HHS / United States R21 AI073103-01A1 / AI / NIAID 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 R01 AI064060 / AI / NIAID NIH HHS / United States A1064060 / / PHS 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 |