KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection.
Killer cell immunoglobulin-like receptors (KIRs) influence both innate and adaptive immunity. But while the role of KIRs in NK-mediated innate immunity is well-documented, the impact of KIRs on the T cell response in human disease is not known. Here we test the hypothesis that an individual's KIR genotype affects the efficiency of their HLA class I-mediated antiviral immune response and the outcome of viral infection. We show that, in two unrelated viral infections, hepatitis C virus and human T lymphotropic virus type 1, possession of the KIR2DL2 gene enhanced both protective and detrimental HLA class I-restricted anti-viral immunity. These results reveal a novel role for inhibitory KIRs. We conclude that inhibitory KIRs, in synergy with T cells, are a major determinant of the outcome of persistent viral infection.
Imperial College, London, United Kingdom.
Nafisa-Katrin
NK
Seich Al Basatena
Aidan
A
Macnamara
Alison M
AM
Vine
Chloe L
CL
Thio
Jacquie
J
Astemborski
Koichiro
K
Usuku
Mitsuhiro
M
Osame
Gregory D
GD
Kirk
Sharyne M
SM
Donfield
James J
JJ
Goedert
Charles R M
CR
Bangham
Mary
M
Carrington
Salim I
SI
Khakoo
Becca
B
Asquith
D005260:Female; D005805:Genes, MHC Class I; D015490:HTLV-I Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D054340:Receptors, KIR / Q000276:immunology; D054343:Receptors, KIR2DL2 / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
D015395:Histocompatibility Antigens Class I; C515077:KIR2DL2 protein, human; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2