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Publication : Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D.

First Author  Campbell JA Year  2007
Journal  J Exp Med Volume  204
Issue  6 Pages  1311-7
PubMed ID  17548517 Mgi Jnum  J:125858
Mgi Id  MGI:3760046 Doi  10.1084/jem.20062026
Citation  Campbell JA, et al. (2007) Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D. J Exp Med 204(6):1311-7
abstractText  NK and T lymphocytes express both activating and inhibiting receptors for various members of the major histocompatibility complex class I superfamily (MHCISF). To evade immunologic cytotoxicity, many viruses interfere with the function of these receptors, generally by altering the displayed profile of MHCISF proteins on host cells. Using a structurally constrained hidden Markov model, we discovered an orthopoxvirus protein, itself distantly class I-like, that acts as a competitive antagonist of the NKG2D activating receptor. This orthopoxvirus MHC class I-like protein (OMCP) is conserved among cowpox and monkeypox viruses, secreted by infected cells, and bound with high affinity by NKG2D of rodents and humans (K(D) approximately 30 and 0.2 nM, respectively). OMCP blocks recognition of host-encoded ligands and inhibits NKG2D-dependent killing by NK cells. This finding represents a novel mechanism for viral interference with NKG2D and sheds light on intercellular recognition events underlying innate immunity against emerging orthopoxviruses.
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