Natural Killer (NK) cells are thought to play a role in the control of viral infection before the establishment of a specific cytolytic T cell response mediated by CD3-positive MHC-restricted T cells. Recently, specific recognition of alloantigens by NK cells was reported. Most of the cells displaying NK activity belong to the CD3-CD16+CD56+ subset of peripheral blood lymphocytes. The mechanism of target cell recognition by NK cells is still unknown.
The aim of this study was (i) to determine whether target cell elements control the recognition and lysis by NK cells, and (ii) to purify a surface molecule from NK cells in sufficient amount to obtain amino-acid sequences. As a first step, it was established that NK clones from a normal individual were able to specifically recognize and kill normal cells from the same individual that had been infected in vitro with human Herpesvirus-6 (HHV-6). The results showed for the first time that specificity in target cell recognition by NK cells is controlled at several levels: first, at the level of the NK clone itself, and second, by genetically variable elements on the target cells that restrict recognition by NK cells. By use of a monoclonal antibody, a NK cell surface protein that is involved in target cell recognition was purified and partial amino-acid sequences were obtained. The ultimate goal of this project is to obtain molecular clones for this molecule and to define its role in target cell recognition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000525-06
Application #
3768822
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Bryceson, Yenan T; Ljunggren, Hans-Gustaf; Long, Eric O (2009) Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors. Blood 114:2657-66
Long, Eric O (2008) Negative signaling by inhibitory receptors: the NK cell paradigm. Immunol Rev 224:70-84
Peterson, Mary E; Long, Eric O (2008) Inhibitory receptor signaling via tyrosine phosphorylation of the adaptor Crk. Immunity 29:578-88
Bryceson, Yenan T; Rudd, Eva; Zheng, Chengyun et al. (2007) Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients. Blood 110:1906-15
Bryceson, Yenan T; March, Michael E; Ljunggren, Hans-Gustaf et al. (2006) Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood 107:159-66
Bryceson, Yenan T; March, Michael E; Ljunggren, Hans-Gustaf et al. (2006) Activation, coactivation, and costimulation of resting human natural killer cells. Immunol Rev 214:73-91
Bryceson, Yenan T; March, Michael E; Barber, Domingo F et al. (2005) Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J Exp Med 202:1001-12
Eissmann, Philipp; Beauchamp, Lisa; Wooters, Joe et al. (2005) Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244). Blood 105:4722-9
Bryceson, Y T; Foster, J A; Kuppusamy, S P et al. (2005) Expression of a killer cell receptor-like gene in plastic regions of the central nervous system. J Neuroimmunol 161:177-82
Barber, Domingo F; Faure, Mathias; Long, Eric O (2004) LFA-1 contributes an early signal for NK cell cytotoxicity. J Immunol 173:3653-9

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