Article: article from journal or magazin.
Influence of HLA-C expression level on HIV control.
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish. PDF type: report
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.
African Americans/genetics, Alleles, Amino Acid Sequence, Anti-Retroviral Agents/therapeutic use, Crohn Disease/genetics, Crohn Disease/immunology, Gene Expression Regulation, HIV/genetics, HIV/immunology, HIV Infections/drug therapy, HIV Infections/genetics, HLA-C Antigens/genetics, Humans, Immunodominant Epitopes/genetics, Molecular Sequence Data, Mutation, Peptide Fragments/immunology, Polymorphism, Single Nucleotide, T-Lymphocytes, Cytotoxic/immunology, Viral Load/genetics
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