title: Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1.
abstract: Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.
authors.affiliation: Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, P.O. Box B, Building 560, Frederick, Maryland 21702, USA.
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Eriko
authors.initials: E
authors.lastname: Yamada
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Sara
authors.initials: S
authors.lastname: Colombo
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Brown
authors.forename: W Lesley
authors.initials: WL
authors.lastname: Shupert
authors.forename: John
authors.initials: J
authors.lastname: Phair
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: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McVicar
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D019562:Viral Load
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D012367:RNA, Viral; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1