Inhibitory KIR and specific HLA-C gene combinations confer susceptibility to or protection against chronic hepatitis B.
Antiviral activity of natural killer (NK) cells is regulated partially through inhibitory and activating killer cell immunoglobulin-like receptors (KIR) interacting with human leukocyte antigen C (HLA-C) ligands. The highly polymorphic nature of HLA-C and KIR genes endows individuals with diverse HLA-C/KIR combinations, which may confer susceptibility to or protection against a certain challenge. We analyzed the genes encoding KIR receptors and HLA-C ligands and HLA-C/KIR combinations in patients with chronic hepatitis B and healthy subjects. We found that inhibitory receptor KIR2DL1 in combination with HLA-C2 ligand confers susceptibility to chronic hepatitis B (CHB), whereas inhibitory receptor KIR2DL3 or KIR2DL3 homozygote in the presence of HLA-C1C1 genotype shows protection against CHB. Our data reveal that inhibitory NK cell interactions are important in determining antiviral immunity and that distinct affinity inhibitory responses will exert different impact on the development of CHB.
Gao
Xuejun
X
Central Laboratory, Shandong Provincial Hospital, Shandong University, Jinan, 250021, PR China.
Jiao
Yulian
Y
Wang
Laicheng
L
Liu
Xiaowen
X
Sun
Wenping
W
Cui
Bin
B
Chen
Zijiang
Z
Zhao
Yueran
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics*; D054342:Receptors, KIR2DL1 / Q000235:genetics; D054343:Receptors, KIR2DL2 / Q000235:genetics; D054344:Receptors, KIR2DL3 / Q000235:genetics; D055815:Young Adult
D015236:HLA-C Antigens; C093100:KIR2DL1 protein, human; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; C496212:KIR2DS1 protein, human; C433932:KIR2DS2 protein, human; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3