The balancing act: inhibitory Ly49 regulate NKG2D-mediated NK cell functions. Semin Immunol 2006 Jun;18(3):186-92
Date
06/02/2006Pubmed ID
16737823Pubmed Central ID
PMC2752866DOI
10.1016/j.smim.2006.04.002Scopus ID
2-s2.0-33744549755 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
NK cells use NKG2D receptor to recognize 'induced-self'. In apparent violation of the 'missing-self' hypothesis, NK cells stimulated through NKG2D can lyse target cells despite normal expression levels of MHC class I molecules. Although, 'overriding' of the inhibitory by the activating signals had been postulated the precise role of inhibitory Ly49 receptors on NKG2D-mediated activation has only started emerging. We propose that NKG2D-mediated activation is a function of 'altering the balance' in the signaling strength between the activating NKG2D and inhibiting Ly49 receptors. Balance in the signaling strength depends on the expression levels of activating ligands on the target cells. Qualitative and quantitative variations of MHC class I molecules expressed on the target cells also plays a major role in determining this 'altered-balance'. Consequently, the nature of Ly49 receptors expressed on specific NK subsets determines the level of NKG2D-mediated NK cell activation. These observations provide a firm basis of 'altered-balance' in NK signaling and describe an active interplay between inhibitory Ly49 and activating NKG2D receptors.
Author List
Malarkannan SAuthor
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Ly
Autoantigens
Histocompatibility Antigens Class I
Humans
Killer Cells, Natural
Lectins, C-Type
Mice
NK Cell Lectin-Like Receptor Subfamily K
Receptors, Immunologic
Receptors, NK Cell Lectin-Like
Receptors, Natural Killer Cell
