Ly49P Recognition of Cytomegalovirus-infected Cells Expressing H2-Dk and CMV-encoded M04 Correlates with the NK Cell Antiviral Response

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2009 Mar 4

PMID 19255146

Citations 81

Authors

Agnieszka Kielczewska

Michal Pyzik

Tianhe Sun

Astrid Krmpotic

Melissa B Lodoen

Michael W Munks

Marina Babic

Ann B Hill

Ulrich H Koszinowski

Stipan Jonjic

Lewis L Lanier

Silvia M Vidal

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) cells are crucial in resistance to certain viral infections, but the mechanisms used to recognize infected cells remain largely unknown. Here, we show that the activating Ly49P receptor recognizes cells infected with mouse cytomegalovirus (MCMV) by a process that requires the presence of H2-D(k) and the MCMV m04 protein. Using H2 chimeras between H2-D(b) and -D(k), we demonstrate that the H2-D(k) peptide-binding platform is required for Ly49P recognition. We identified m04 as a viral component necessary for recognition using a panel of MCMV-deletion mutant viruses and complementation of m04-deletion mutant (Deltam04) virus infection. MA/My mice, which express Ly49P and H2-D(k), are resistant to MCMV; however, infection with Deltam04 MCMV abrogates resistance. Depletion of NK cells in MA/My mice abrogates their resistance to wild-type MCMV infection, but does not significantly affect viral titers in mice infected with Deltam04 virus, implicating NK cells in host protection through m04-dependent recognition. These findings reveal a novel mechanism of major histocompatibility complex class I-restricted recognition of virally infected cells by an activating NK cell receptor.

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