Disease relevance of KLRA1

• Critical Residues at the Ly49 Natural Killer Receptor's Homodimer Interface Determine Functional Recognition of m157, a Mouse Cytomegalovirus MHC Class I-Like Protein [1].

High impact information on KLRA1

• Whereas the human killer cell inhibitory receptors (KIRs) for HLA class I are immunoglobulin-like monomeric type I glycoproteins, the murine Ly49 receptors for H-2 are type II homodimers of the C-type lectin superfamily [2].
• The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity [3].
• We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes [3].
• Recent advances indicate that immunoreceptor tyrosine-based inhibitory motifs in the cytoplasmic domains of the killer cell inhibitory receptors and Ly-49 receptors recruit the SH2-containing protein tyrosine phosphatases, SHP-1 and SHP-2, resulting in inhibition of natural-killer- and T-cell-mediated cytotoxicity and cytokine secretion [4].
• Ly-49-driven mobilization of LFA-1 adhesive function may represent a fundamental proximal event during NK cell interactions with target cells involving activating Ly-49 receptors, leading to target cell death [5].

Biological context of KLRA1

• Identification of a human member of the Ly-49 multigene family [6].
• PCR screening of a 22-clone yeast artificial chromosome contig localized the LY49L locus to the human NK gene complex on chromosome 12p12-p13 [6].
• Inhibitory natural killer receptors (NKRs) such as killer cell immunoglobulin-like receptors (KIRs) in humans and Ly49 molecules in mice are expressed on NK cells and recognize multiple major histocompatibility (MHC) class I proteins [7].
• The antisense transcripts generated in the Ly49 genes are far removed from the promoter responsible for Ly49 expression in mature NK cells, whereas the antisense KIR transcripts detected are within the adult promoter region [8].
• Single amino acid substitutions in the B-pocket that did not prevent peptide binding disrupted Ly49 recognition [9].

Anatomical context of KLRA1

• As demonstrated by Northern blot analysis, Ly-49L was transcribed by IL-2-activated NK cells, but not by freshly isolated B or T cells [6].
• NK cell function is regulated by Ly49 receptors in mice and killer cell Ig-like receptors in humans [1].
• Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b) [3].
• Furthermore, we show that baboon lymphocytes express both full-length Ly49L transcripts and multiple KIR genes [10].
• Nevertheless, we noted that the usage of MHC class I-specific Ly49 family receptors was significantly altered in the absence of T and/or B cells [11].

Physical interactions of KLRA1

• In the mouse, receptors encoded by genes of the Ly-49 family bind certain polymorphic H-2 molecules and prevent lysis of normal hematopoietic cell targets [12].

Other interactions of KLRA1

• In addition, in the course of these studies several EST sequences were localized in the region, one immediately upstream of the LY49L gene [13].
• In this part we have mapped the human LY49L gene, a homologue of the rodent Ly49 genes, which encode important MHC class I receptors for the regulation of NK cell activity in rodents [13].

Analytical, diagnostic and therapeutic context of KLRA1

• Southern blot analysis of genomic DNA showed a simple pattern with a full-length Ly-49L probe at low stringency hybridization conditions, suggesting that Ly-49L may be the only human member of the Ly-49 multigene family [6].
• Presently we review the genetics and biology of natural transplantation processes in colonial tunicates, comparing it with allorecognition as mediated through the vertebrate T-cell receptor, killer cell inhibitory receptor/Ly49, and MHC [14].

References