Chapter

Immunobiology of Natural Killer Cell Receptors

Volume 298 of the series Current Topics in Microbiology and Immunology pp 207-223

NK Cell Receptors Involved in the Response to Human Cytomegalovirus Infection

  • M. GumáAffiliated withMolecular Immunopathology Unit, DCEXS, Universitat Pompeu Fabra
  • , A. AnguloAffiliated withInstitut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS)
  • , M. López-BotetAffiliated withMolecular Immunopathology Unit, DCEXS, Universitat Pompeu Fabra Email author 

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Abstract

Human cytomegalovirus (HCMV) infection is a paradigm of the complexity reached by host-pathogen interactions. To avoid recognition by cytotoxic T lymphocytes (CTL) HCMV inhibits the expression of HLA class I molecules. As a consequence, engagement of inhibitory killer immunoglobulin-like receptors (KIR), CD94/NKG2A, and CD85j (ILT2 or LIR-1) natural killer cell receptors (NKR) specific for HLA class I molecules is impaired, and infected cells become vulnerable to an NK cell response driven by activating receptors. In addition to the well-defined role of the NKG2D lectin-like molecule, the involvement of other triggering receptors (i.e., activating KIR, CD94/NKG2C, NKp46, NKp44, and NKp30) in the response to HCMV is being explored. To escape from NK cell-mediated surveillance, HCMV interferes with the expression of NKG2D ligands in infected cells. In addition, the virus may keep NK inhibitory receptors engaged preserving HLA class I molecules with a limited role in antigen presentation (i.e., HLA-E) or, alternatively, displaying class I surrogates. Despite considerable progress in the field, a number of issues regarding the involvement of NKR in the innate immune response to HCMV remain uncertain.