Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158)

被引:119
作者
Long, EO
Barber, DF
Burshtyn, DN
Faure, M
Peterson, M
Rajagopalan, S
Renard, V
Sandusky, M
Stebbins, CC
Wagtmann, N
Watzl, C
机构
[1] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA
[2] Univ Alberta, Dept Med Microbiol & Immunol, Heritage Med Res Ctr, Edmonton, AB T6G 2M7, Canada
[3] M&E Biotech, Copenhagen, Denmark
[4] Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark
关键词
D O I
10.1034/j.1600-065X.2001.1810119.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The killer cell immunoglobulin-like receptor (KIR) family includes receptors that bind to HLA class I molecules on target cells and inhibit natural killer (NK)-cell cytotoxicity, and receptors such as KIR3DL7 with no known ligand and function. Inhibitory KIR recruit the tyrosine phosphatase SHP-1 to block signals transduced by any one of a number of activation receptors. Inhibition of overall protein tyrosine phosphorylation by SHP-1 during binding of KIR to MHC class I on target cells is selective, suggesting that a limited number of substrates a-re dephosphorylated by SHP-1. We have chosen to study KIR inhibition as it occurs during binding of KIR to MHC class I on target cells, despite the technical limitations inherent to studies of processes regulated by cell contact. KIR binding to MHC class I on target cells inhibits tyrosine phosphorylation of the activation receptor 2B4 (CD244) and disrupts adhesion of NK cells to target cells. Inhibition of proximal events in NK activation may increase the availability of NK cells by liberating them from non-productive interactions with resistant target cells. As the receptors and the signaling pathways that induce NK cytotoxicity a-re not fully characterized, elucidation of the inhibitory mechanism employed by KIR may provide insight into NK activation.
引用
收藏
页码:223 / 233
页数:11
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