Abstract
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.
Highlights
Killer cell immunoglobulin-like receptors (KIRs) are a family of transmembrane proteins that are expressed on natural killer (NK) cells and subsets of T cells [1,2,3]
We have found that a gene that encodes a receptor (KIR2DL2) enhances both protective and detrimental HLA class I-mediated immunity to hepatitis C virus (HCV) and human T lymphotropic virus type 1 (HTLV-1)
KIRs are primarily associated with innate immunity, our observations suggest that they have a major impact on the efficiency of the adaptive immune response
Summary
Killer cell immunoglobulin-like receptors (KIRs) are a family of transmembrane proteins that are expressed on natural killer (NK) cells and subsets of T cells [1,2,3]. They bind HLA class I molecules and have activatory and inhibitory isoforms [4]. KIRs contribute directly and indirectly to antiviral immunity. KIRs on NK cells sense the loss of HLA class I molecules from the cell surface and trigger NK-mediated cytolysis. HLA class I molecules can be grouped into allotypes with similar KIR binding properties [8]. KIR2DL2 binds group C1 HLA-C molecules which have asparagine at residue 80, and, with a weaker affinity, group C2 molecules which have a lysine at position 80 [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
