NK cell education via nonclassical MHC and non-MHC ligands

Ly-49s3 is a promiscuous activating rat NK cell receptor for nonclassical MHC class I-encoded target ligands.

Previous studies of the rapid rejection of MHC-disparate lymphocytes in rats, named allogeneic lymphocyte cytotoxicity, have indicated that rat NK cells express activating receptors for nonclassical MHC class I allodeterminants from the RT1-C/E/M region. Using an expression cloning system that identifies activating receptors associated with the transmembrane adapter molecule DAP12, we have clon...

Follow the Leader: NK Cell Receptors for Classical and Nonclassical MHC Class I

and KIR3D molecules are heterogeneous. Isoforms with long cytoplasmic tails (i.e., KIR2DL and KIR3DL) contain ITIM that bind SHP-1 and inactivate NK cells. KIRs with short cytoplasmic domains (KIR2DS and KIR3DS) lack ITIM, but possess charged amino acids in their trans-membrane segments that permit association with DAP12, a membrane receptor expressing an immunoreceptor tyrosine-based activatio...

HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors.

Killer Ig-like receptors (KIRs) are innate immune receptors expressed by NK and T cells classically associated with the detection of missing self through loss of their respective MHC ligand. Some KIR specificities for allelic classical class I MHC (MHC-I) have been described, whereas other KIR receptor-ligand relationships, including those associated with nonclassical MHC-I, have yet to be clea...

Ly49-dependent NK cell licensing and effector inhibition involve the same interaction site on MHC ligands.

NK cells become functionally competent to be triggered by their activation receptors through the interaction of NK cell inhibitory receptors with their cognate self-MHC ligands, an MHC-dependent educational process termed "licensing." For example, Ly49A(+) NK cells become licensed by the interaction of the Ly49A inhibitory receptor with its MHC class I ligand, H2D(d), whereas Ly49C(+) NK cells ...

Are Ligands for NK Cell Ig-like Receptors HLA-F and MHC Class I Open Conformers