Disease relevance of Klra3

• Since NK-1.1 and NK-2.1 are also expressed on 2-3% of spleen cells of positive strains we suggest that all three alloantigens identify the NK cells in normal mouse spleen which lyse the lymphoma target cell line YAC [1].

High impact information on Klra3

• We show here that the Ly49A and Ly49C NK-cell receptors are each subject to allelic exclusion [2].
• Expression of Ly49A and Ly49C, another member of the Ly49 family with distinct MHC specificity, define subpopulations of NK cells that are only partly overlapping [2].
• During the first days after birth, few or no splenic NK cells express Ly49A, Ly49C, Ly49G2, or Ly49I receptors [3].
• Flow cytometric analyses of COS cells transfected with the two cDNAs showed that the 5E6 antibody binds to both Ly-49 molecules, while another anti-Ly-49C antibody, 4LO3311, binds to the newly described Ly-49C but not the previously reported Ly-49CB6 [4].
• Thus, there appears to be allelic exclusion of 5E6 expression that may be related to the ability of F1 hybrid mice to reject parental H-2d bone marrow cell grafts [5].

Biological context of Klra3

• Gene order and intergene distances (in cM) were: centromere-Cd94/Nkg2d-(0.05)-Ly49a/Ly49c/Ly49 g/Cmv1-(0. 3)-Prp/Kap/D6Mit13/111/219 [6].
• 5E6 is nearly identical to Ly-49C; the deduced amino acid sequence reveals a polypeptide of 266 amino acids with a molecular weight of 31,284 that contains multiple cysteine residues to explain its disulfide-linked homodimer structure and five potential N-linked glycosylation sites [5].
• Here, we isolated and cloned the gene encoding 5E6 and determined the nucleotide sequence of the cDNA [5].
• Chromosomal mapping indicates that 5E6 is located within the NK gene complex on chromosome 6 [5].
• Blockade of Ly49C and I inhibitory receptors using F(ab')(2) fragments of the 5E6 monoclonal antibody (mAb) resulted in increased cytotoxicity against syngeneic tumors and decreased tumor cell growth in vitro [7].

Anatomical context of Klra3

• These results suggest that reduction of Ly49C/I+ NK1.1+gamma/delta T cells in beta2m+/+ mice is at least partly due to the down-modulation by MHC class I molecules on BM-derived haematopoietic cells or radioresistant cells in the thymus [8].
• The antibodies 5E6 and 34-1-2S (anti-class I MHC) inhibited the binding of Ly-49C to an H-2s cell line [9].
• In addition, we find a several-fold increase in Ly49C/I-expressing NKT cells in adult thymus, apparently independent of MHC class I molecules [10].
• This NK-1.1- CD3- LFA-3+ B220+ population, when stimulated with IL-2 and co-cultured with supportive syngeneic stromal cells, generated populations of NK-1.1+ Ly49A+ Ly49C/I+ CD3- mature natural killer cells [11].

Associations of Klra3 with chemical compounds

• With two other targets, E male G2 and RBL-5, neither serum produced significant depletion of activity, Analysis of SC indirectly labeled with either NK-1.1 or NK-2.1 antiserum and fluorescein-labeled goat anti-mouse Ig, however, did not detect significant differences between NK-1+ and NK-2+ cell populations [12].
• 2) The NK(YAC-1) precursors lack the surface antigens (NK-2.1, asialo GM1, Qa-5, Thy-1) that are characteristically seen on mature NK cells [13].
• Unlike NK cells, the cells capable of lysing FLD-3 cells in vitro were insensitive to antibodies directed against NK-2.1 or Thy-1.2 antigens (plus complement) and to pretreatment of mice in vivo with silica particles, 89Sr or estradiol [14].
• The former mAbs recognized epitopes present on CaE major allergen and also shared by other components. mAb 5E6 showed a spread reactivity on CaE, with exclusion of the major allergen [15].

Other interactions of Klra3

• Using a site-directed mutagenesis approach, we have targeted residues conserved in receptors binding to m157 (Ly49H and Ly49I(129)) but different from receptors lacking m157 recognition (Ly49C, Ly49I(B6), and Ly49U) [16].
• In this manner, we identified five new potential Ly49 genes which have been tentatively termed Ly49j-n. Ly49j, k, and n belong to the Ly49c-related subfamily, whereas Ly49l and Ly49m are most similar to Ly49d and g, respectively [17].
• 5E6 is a cell surface molecule expressed on a subpopulation of murine natural killer (NK) cells that are involved in the specific rejection of H-2d or H-2f (hemopoietic histocompatibility determinant 2) bone marrow cell grafts [5].
• The expression levels of H60 on the target cells determined the extent to which the inhibition by Ly49C/I receptors can be overridden [18].
• Over 75% of them expressed Ly49C, I, or NKG2A, which are thought to recognize self-class I MHC (H-2b) [19].

Analytical, diagnostic and therapeutic context of Klra3

• Here we show by Southern blotting that at least two additional new sequences exist in C57BL/6 mice that are also closely related to Ly49c in the carbohydrate recognition domain [17].
• Treatment of leukemia-bearing mice with 5E6 F(ab')(2) fragments or adoptive transfer of NK cells treated ex vivo with the F(ab')(2) resulted in significant increases in survival [7].
• Therefore, down-regulation of developing Ly49A+ and Ly49C/I+ chimeric NK cell frequencies by cognate ligands within 7-8 wk after BM transplantation may be important for successful engraftment [20].
• Cross-reactivity was evaluated by ELISA inhibition and immunoblotting. mAbs 2D5 and 4A6 recognized periodate-resistant epitopes, whereas the mAb 5E6 reacted with a periodate-sensitive determinant [15].
• We show that treatment of interleukin 2-activated C57BL/6 (B6, H2b) SCID-mouse NK cells with 5E6 F(ab')2 fragments during 48-hour coculture resulted in autoreactivity against syngeneic BMCs as demonstrated by suppression of myeloid reconstitution on day 14 post-BMT [21].

References