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The human cytomegalovirus MHC class I homolog UL18 inhibits LIR-1+ but activates LIR-1- NK cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Apr 01; Vol. 178 (7), pp. 4473-81. - Publication Year :
- 2007
-
Abstract
- The inhibitory leukocyte Ig-like receptor 1 (LIR-1, also known as ILT2, CD85j, or LILRB1) was identified by its high affinity for the human CMV (HCMV) MHC class I homolog gpUL18. The role of this LIR-1-gpUL18 interaction in modulating NK recognition during HCMV infection has previously not been clearly defined. In this study, LIR-1(+) NKL cell-mediated cytotoxicity was shown to be inhibited by transduction of targets with a replication-deficient adenovirus vector encoding UL18 (RAd-UL18). Fibroblasts infected with an HCMV UL18 mutant (DeltaUL18) also exhibited enhanced susceptibility to NKL killing relative to cells infected with the parental virus. In additional cytolysis assays, UL18-mediated protection was also evident in the context of adenovirus vector transduction and HCMV infection of autologous fibroblast targets using IFN-alpha-activated NK bulk cultures derived from a donor with a high frequency of LIR-1(+) NK cells. A single LIR-1(high) NK clone derived from this donor was inhibited by UL18, while 3 of 24 clones were activated. CD107 mobilization assays revealed that LIR-1(+) NK cells were consistently inhibited by UL18 in all tested donors, but this effect was often masked in the global response by UL18-mediated activation of a subset of LIR-1(-) NK cells. Although Ab-blocking experiments support UL18 inhibition being induced by a direct interaction with LIR-1, the UL18-mediated activation is LIR-1 independent.
- Subjects :
- Adenoviridae genetics
Antigens, CD analysis
Antigens, CD immunology
Capsid Proteins genetics
Cells, Cultured
Cytotoxicity, Immunologic
Genetic Vectors genetics
Histocompatibility Antigens Class I genetics
Humans
Killer Cells, Natural chemistry
Leukocyte Immunoglobulin-like Receptor B1
Lymphocyte Activation
Receptors, Immunologic analysis
Receptors, Immunologic immunology
Sequence Deletion
Capsid Proteins immunology
Histocompatibility Antigens Class I immunology
Killer Cells, Natural immunology
Receptors, Immunologic antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 178
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17372005
- Full Text :
- https://doi.org/10.4049/jimmunol.178.7.4473