title: 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.
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Apps
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Carlson
authors.forename: Haoyan
authors.initials: H
authors.lastname: Chen
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yuki
authors.forename: Greg Q
authors.initials: GQ
authors.lastname: Del Prete
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: Mina
authors.initials: M
authors.lastname: John
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: George
authors.initials: G
authors.lastname: Nelson
authors.forename: Ronald
authors.initials: R
authors.lastname: Bosch
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Judy L
authors.initials: JL
authors.lastname: Stein
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Soderberg
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.forename: Xue
authors.initials: X
authors.lastname: Zeng
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fang
authors.forename: Ashley
authors.initials: A
authors.lastname: Moffett
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Paul
authors.initials: P
authors.lastname: McLaren
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Bruce
authors.initials: B
authors.lastname: Walker
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Amy
authors.initials: A
authors.lastname: Weintrob
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load / Q000235:genetics
chemical_list: D044966:Anti-Retroviral Agents; D015236:HLA-C Antigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments
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