Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1.
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.
Martin
Maureen P
MP
Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, P.O. Box B, Building 560, Frederick, Maryland 21702, USA.
Qi
Ying
Y
Gao
Xiaojiang
X
Yamada
Eriko
E
Martin
Jeffrey N
JN
Pereyra
Florencia
F
Colombo
Sara
S
Brown
Elizabeth E
EE
Shupert
W Lesley
WL
Phair
John
J
Goedert
James J
JJ
Buchbinder
Susan
S
Kirk
Gregory D
GD
Telenti
Amalio
A
Connors
Mark
M
O'Brien
Stephen J
SJ
Walker
Bruce D
BD
Parham
Peter
P
Deeks
Steven G
SG
McVicar
Daniel W
DW
Carrington
Mary
M
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
D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D012367:RNA, Viral; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1