Influence of HLA-C expression level on HIV control.
Abstract
A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant
genome-wide effect on HIV control in European Americans and is also associated with
the level of HLA-C expression. We characterized the differential cell surface expression
levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression
on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was
associated with protection against multiple outcomes independently of individual HLA
allelic effects in both African and European Americans, regardless of their distinct
HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression
was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency
of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect
in Crohn's disease, suggesting a broader influence of HLA expression levels in human
disease.
Type
Journal articleSubject
African AmericansAlleles
Amino Acid Sequence
Anti-Retroviral Agents
Crohn Disease
Gene Expression Regulation
HIV
HIV Infections
HLA-C Antigens
Humans
Immunodominant Epitopes
Molecular Sequence Data
Mutation
Peptide Fragments
Polymorphism, Single Nucleotide
T-Lymphocytes, Cytotoxic
Viral Load
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https://hdl.handle.net/10161/14728Published Version (Please cite this version)
10.1126/science.1232685Publication Info
Apps, Richard; Qi, Ying; Carlson, Jonathan M; Chen, Haoyan; Gao, Xiaojiang; Thomas,
Rasmi; ... Carrington, Mary (2013). Influence of HLA-C expression level on HIV control. Science, 340(6128). pp. 87-91. 10.1126/science.1232685. Retrieved from https://hdl.handle.net/10161/14728.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Michael Anthony Moody
Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious
Diseases and Professor in the Department of Integrative Immunobiology at Duke University
Medical Center. Research in the Moody lab is focused on understanding the B cell responses
during infection, vaccination, and disease. The lab has become a resource for human
phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine
Institute (DHVI). The Moody lab is currently funded to study in
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