Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Widespread impact of HLA restriction on immune control and escape pathways of HIV-1
Journal of Virology, Volume 86, No. 9, Year 2012
Notification
URL copied to clipboard!
Description
The promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 instances of differential escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine. © 2012, American Society for Microbiology.
Authors & Co-Authors
Carlson, Jonathan M.
United States, Redmond
Microsoft Research
Listgarten, Jennifer
United States, Redmond
Microsoft Research
Pfeifer, Nico
United States, Redmond
Microsoft Research
Tan, Vincent Y.F.
United States, Redmond
Microsoft Research
Kadie, Carl M.
United States, Redmond
Microsoft Research
Walker, Bruce D.
United States, Cambridge
Massachusetts Institute of Technology
United States, Chevy Chase
Howard Hughes Medical Institute
South Africa, Durban
The Nelson R. Mandela Medical School
Ndung'u, Thumbi P.
United States, Cambridge
Massachusetts Institute of Technology
South Africa, Durban
The Nelson R. Mandela Medical School
Shapiro, Roger L.
United States, Boston
Beth Israel Deaconess Medical Center
Frater, John
United Kingdom, Oxford
Nuffield Department of Medicine
Brumme, Zabrina L.
Canada, Burnaby
Simon Fraser University
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Goulder, Philip Jeremy Renshaw
South Africa, Durban
The Nelson R. Mandela Medical School
United Kingdom, Oxford
University of Oxford
Heckerman, David E.
United States, Redmond
Microsoft Research
Statistics
Citations: 132
Authors: 12
Affiliations: 9
Identifiers
Doi:
10.1128/JVI.06728-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Genetics And Genomics
Infectious Diseases