Prod'homme, Virginie, Griffin, Cora, Aicheler, Rebecca, Wang, Edward Chung Yern, McSharry, Brian Patrick, Rickards, Carole Ruth, Stanton, Richard James, Borysiewicz, Leszek K., Lopez-Botet, Miguel, Wilkinson, Gavin William Grahame and Tomasec, Peter 2007. The Human Cytomegalovirus MHC Class I Homolog UL18 Inhibits LIR-1+ but Activates LIR-1- NK Cells. The Journal of Immunology 178 (7) , pp. 4473-4481. |
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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine Systems Immunity Research Institute (SIURI) |
Publisher: | American Association of Immunologists |
ISSN: | 0022-1767 |
Last Modified: | 28 Jun 2019 02:41 |
URI: | http://orca-mwe.cf.ac.uk/id/eprint/294 |
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