Title | HIV escape mutations occur preferentially at HLA-binding sites of CD8 T-cell epitopes. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Bronke C, Almeida C-AM, McKinnon E, Roberts SG, Keane NM, Chopra A, Carlson JM, Heckerman D, Mallal S, John M |
Journal | AIDS |
Volume | 27 |
Issue | 6 |
Pagination | 899-905 |
Date Published | 2013 Mar 27 |
ISSN | 1473-5571 |
Keywords | Binding Sites, Epitopes, T-Lymphocyte, HIV-1, Humans, Immune Evasion, Mutation, Missense, Phosphoproteins, Polymorphism, Genetic, Protein Binding |
Abstract | OBJECTIVE: To define the relative frequencies of different mechanisms of viral escape. DESIGN: A population-based approach to examine the distribution of HIV polymorphism associated with diverse population human leucocyte antigens (HLAs) at sites within and flanking CD8 T-cell epitopes as a correlate of likely mechanisms of viral escape. METHODS: Sequence windows surrounding 874 HLA allele-specific polymorphisms across the full HIV-1 proteomic consensus sequence were scanned by an epitope-prediction programme. Either already known or probable CD8 T-cell epitopes with HLA restriction matching that of the proximal HLA association were identified and synthesized. These peptides were used as stimulating antigens in automated enzyme-linked immunospot (ELISpot) assays. Peptide arrays were customized to each individual based on their HLA genotype. RESULTS: Among HLA-associated HIV polymorphisms detected in the viral sequences of a cohort of 800 individuals with chronic subtype B HIV infection, those which were likely to affect HLA peptide binding were significantly more common than polymorphisms at nonanchor HLA binding sites. HIV epitopes with such polymorphisms were associated with reduced IFNγ responses in ELISpot assays. HIV escape at sites affecting T-cell receptor (TCR) engagement and epitope processing were also evident. CONCLUSION: HIV escape from HLA-peptide binding predominates as an effective viral evasion strategy and therefore has implications for inclusion of HLA-adapted epitopes in vaccine immunogens. |
DOI | 10.1097/QAD.0b013e32835e1616 |
Alternate Journal | AIDS |
PubMed ID | 23276808 |
PubMed Central ID | PMC3818524 |
Grant List | AI-68636 / AI / NIAID NIH HHS / United States AI046376 / AI / NIAID NIH HHS / United States AI069419 / AI / NIAID NIH HHS / United States AI069424 / AI / NIAID NIH HHS / United States AI069432 / AI / NIAID NIH HHS / United States AI069434 / AI / NIAID NIH HHS / United States AI069439 / AI / NIAID NIH HHS / United States AI069447 / AI / NIAID NIH HHS / United States AI069450 / AI / NIAID NIH HHS / United States AI069452 / AI / NIAID NIH HHS / United States AI069471 / AI / NIAID NIH HHS / United States AI069472 / AI / NIAID NIH HHS / United States AI069474 / AI / NIAID NIH HHS / United States AI069477 / AI / NIAID NIH HHS / United States AI069484 / AI / NIAID NIH HHS / United States AI069495 / AI / NIAID NIH HHS / United States AI069501 / AI / NIAID NIH HHS / United States AI069502 / AI / NIAID NIH HHS / United States AI069513 / AI / NIAID NIH HHS / United States AI069532 / AI / NIAID NIH HHS / United States AI069556 / AI / NIAID NIH HHS / United States AI25859 / AI / NIAID NIH HHS / United States AI27661 / AI / NIAID NIH HHS / United States AI27673 / AI / NIAID NIH HHS / United States AI32782 / AI / NIAID NIH HHS / United States AI34853 / AI / NIAID NIH HHS / United States AI38858 / AI / NIAID NIH HHS / United States AI46370 / AI / NIAID NIH HHS / United States AI64086 / AI / NIAID NIH HHS / United States AI68634 / AI / NIAID NIH HHS / United States AI68636 / AI / NIAID NIH HHS / United States AI69411 / AI / NIAID NIH HHS / United States AI69423 / AI / NIAID NIH HHS / United States AI69465 / AI / NIAID NIH HHS / United States AI69467 / AI / NIAID NIH HHS / United States AI69494 / AI / NIAID NIH HHS / United States R01 AI060460 / AI / NIAID NIH HHS / United States R01 AI060460 / AI / NIAID NIH HHS / United States RR024975 / RR / NCRR NIH HHS / United States UM1 AI069423 / AI / NIAID NIH HHS / United States |