HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.
Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.
Khakoo
Salim I
SI
Liver Group, Division of Infection, Inflammation, and Repair, Southampton University, Southampton 5016 6YD, UK. sik@soton.ac.uk
Thio
Chloe L
CL
Martin
Maureen P
MP
Brooks
Collin R
CR
Gao
Xiaojiang
X
Astemborski
Jacquie
J
Cheng
Jie
J
Goedert
James J
JJ
Vlahov
David
D
Hilgartner
Margaret
M
Cox
Steven
S
Little
Ann-Margeret
AM
Alexander
Graeme J
GJ
Cramp
Matthew E
ME
O'Brien
Stephen J
SJ
Rosenberg
William M C
WM
Thomas
David L
DL
Carrington
Mary
M
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D001803:Blood Transfusion; D002648:Child; D015331:Cohort Studies; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000635:transmission / Q000821:virology; D006720:Homozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008297:Male; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D012044:Regression Analysis; D044465:White People / Q000235:genetics
D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3