‘Unlicensed’ natural killer cells dominate the response to cytomegalovirus infection

Mark T Orr. et al 2010 Nat. Immunology 11, 321-327

Speaker: Jhih-Sin Lu (陸致信)                              Time: 13:00~14:00,Oct 6, 2010

Commentator: Dr.Yee-Shin Lin (林以行老師)     Place: Room 601

Abstract:

Natural killer (NK) cells played a important role in innate immunity against microorganism infection and tumor formation. The activation of NK cell is dependent on stimulatory and inhibitory signaling from target cell, but the mechanism of self-tolerance in NK cell is still in controversy. [l] The previous studies show that NK cell expressed the receptor of MHC class I molecules had higher activity after activation. Thus the NK cell without receptor of MHC class I molecules had been defined as “unlicensed NK cell”, the unlicensed NK cell is also more hyporesponsive after activation in vitro and in vivo without infection [2]. But other studies show that both unlicensed and licensed NK cell is fully activated in virus infection, it implied that licensing of NK cell is not required for NK cell activation in some condition [3]. Based on previous study in NK cell, author hypothesized that licensed and unlicensed NK cell existed different capability against CMV infection. In this study author found that unlicensed NK cell without inhibitory receptor (Ly49C/I) is higher responsive when countered with the target cell expressed MHC class I molecules. The proliferation of licensed NK cell had been limited by Ly49C/I-mediated suppression and SHP1. In the animal model, it had been demonstrated that unlicensed rather than licensed NK cell protect neonates from CMV infection. The result of this study indicated NK licensing is not benefit to host for the protection of virus infection.

References:

1.       Eric O. Long et al Negative signaling by inhibitory receptors: the NK cell paradigm. Immunol. Rev. 224: 70–84 (2008)

2.       Sungjin Kim et al Licensing of natural killer cells by host major histocompatibility complex class I molecules Nat. 436: 709-713

3.      Fernandez, N.C. et al. A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105: 4416–4423 (2005)