Document Detail


HIV escape mutations occur preferentially at HLA-binding sites of CD8 T-cell epitopes.
MedLine Citation:
PMID:  23276808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Corine Bronke; Coral-Ann M Almeida; Elizabeth McKinnon; Steven G Roberts; Niamh M Keane; Abha Chopra; Jonathan M Carlson; David Heckerman; Simon Mallal; Mina John
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  27     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-05-24     Completed Date:  2013-10-24     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  899-905     Citation Subset:  IM; X    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00031408;  NCT00050895
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Epitopes, T-Lymphocyte / genetics,  immunology*
HIV-1 / genetics,  immunology*,  metabolism
Humans
Immune Evasion*
Mutation, Missense*
Phosphoproteins / immunology*,  metabolism
Polymorphism, Genetic
Protein Binding
Grant Support
ID/Acronym/Agency:
AI-68636/AI/NIAID NIH HHS; AI046376/AI/NIAID NIH HHS; AI069419/AI/NIAID NIH HHS; AI069424/AI/NIAID NIH HHS; AI069432/AI/NIAID NIH HHS; AI069434/AI/NIAID NIH HHS; AI069439/AI/NIAID NIH HHS; AI069447/AI/NIAID NIH HHS; AI069450/AI/NIAID NIH HHS; AI069452/AI/NIAID NIH HHS; AI069471/AI/NIAID NIH HHS; AI069472/AI/NIAID NIH HHS; AI069474/AI/NIAID NIH HHS; AI069477/AI/NIAID NIH HHS; AI069484/AI/NIAID NIH HHS; AI069495/AI/NIAID NIH HHS; AI069501/AI/NIAID NIH HHS; AI069502/AI/NIAID NIH HHS; AI069513/AI/NIAID NIH HHS; AI069532/AI/NIAID NIH HHS; AI069556/AI/NIAID NIH HHS; AI25859/AI/NIAID NIH HHS; AI27661/AI/NIAID NIH HHS; AI27673/AI/NIAID NIH HHS; AI32782/AI/NIAID NIH HHS; AI34853/AI/NIAID NIH HHS; AI38858/AI/NIAID NIH HHS; AI46370/AI/NIAID NIH HHS; AI64086/AI/NIAID NIH HHS; AI68634/AI/NIAID NIH HHS; AI68636/AI/NIAID NIH HHS; AI69411/AI/NIAID NIH HHS; AI69423/AI/NIAID NIH HHS; AI69465/AI/NIAID NIH HHS; AI69467/AI/NIAID NIH HHS; AI69494/AI/NIAID NIH HHS; R01 AI060460/AI/NIAID NIH HHS; R01 AI060460/AI/NIAID NIH HHS; RR024975/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Epitopes, T-Lymphocyte; 0/La protein, human; 0/Phosphoproteins
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