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The UL16‐binding proteins, a novel family of MHC class I‐related ligands for NKG2D, activate natural killer cell functions
Author(s) -
Sutherland Claire L.,
Chalupny N. Jan,
Cosman David
Publication year - 2001
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2001.1810115.x
Subject(s) - nkg2d , biology , mhc class i , microbiology and biotechnology , natural killer cell , janus kinase 3 , major histocompatibility complex , immune system , t cell , immunology , interleukin 21 , cytotoxic t cell , biochemistry , in vitro
Summary: The UL16‐binding proteins (ULBPs) are a novel family of MHC class I‐related molecules (MICs) that were identified based on their ability to bind to the human cytomegalovirus (HCMV) glycoprotein UL16. UL16 also binds to a member of another family of MHC class I‐like molecules, MICB. The ULBPs and MICs are ligands for NKG2D/DAP10, an activating receptor expressed by natural killer (NK) cells and other immune effector cells, and this interaction can be blocked by UL16. Engagement of NKG2D/DAP10 by ULBPs or MICs expressed on a target cell can overcome an inhibitory signal generated by NK‐cell recognition of MHC class I molecules and trigger NK cytotoxicity. ULBPs elicit their effects on NK cells by activating the janus kinase 2, signal transducer and activator of transcription 5, extracellular‐signal‐regulated kinase mitogen‐activated protein kinase and Akt/protein kinase B signal transduction pathways. Although ULBPs alone activate multiple signaling pathways and induce modest cytokine production, ULBPs synergize strongly with interleukin‐12 for production of interferon‐γ by NK cells. This finding is consistent with reports in T cells that NKG2D/DAP10 can act as a co‐stimulatory receptor in a similar manner as CD28. The possible roles of ULBPs in mediating immune responses to viruses and tumors and the potential mechanisms by which UL16 may allow HCMV to evade immune detection are areas of active investigation. We thank Gary Carlton for assistance with figures and Anne Aumell for editorial assistance.