Disease relevance of KIR2DS2

• Moreover, the KIR2DS2 gene, which encodes for CD158j, is a genetic risk factor for rheumatoid vasculitis [1].
• Characteristics of binding of Escherichia coli serotype O157:H7 strain CL-49 to purified intestinal mucin [2].

High impact information on KIR2DS2

• We also report the 2.3-A structure of KIR2DS2, which reveals subtle displacements of two residues (Tyr45 and Gln71) involved in the interaction of KIR2DL2 with HLA-Cw3 [3].
• Crystal structure of the human natural killer cell activating receptor KIR2DS2 (CD158j) [3].
• CD4(+)CD28(null) T cell clones isolated from RA patients with vasculitis were found to express killer cell immunoglobulin-like receptors (KIRs) with the stimulatory KIR2DS2 often present in the absence of opposing inhibitory receptors with related specificities [4].
• Specifically, KIR2DS2 in conjunction with the appropriate HLA-C ligand may have a role in vascular damage by regulating CD4(+)CD28(null) T cells [4].
• Moreover, this effect is seen only when the donor additionally carries the activating KIR gene KIR2DS2 (P =.045) [5].

Biological context of KIR2DS2

• The genes KIR3DL1, KIR2DS4 and KIR2DL3 were present on 31, 32 and 15 different B haplotypes, respectively, and 64, 65 and 40 of the total B haplotypes, respectively [6].
• Three particular receptors, KIR2DS2, KIR2DL2, and KIR3DL2, had significant differences in gene expression frequencies between the clone families [7].
• Patients were grouped according to their donors' activating KIR genotype including two loci: KIR2DS1 and KIR2DS2 [8].
• Senescence of effector CD4(+) T cells is associated with the loss of CD28 and the de novo expression of KIR2DS2, NKG2D, and CX(3)CR1, all of which function as costimulatory molecules and reduce the threshold for T-cell activation [9].
• Purified sHLA-Cw3 or -Cw4 alleles, isolated from the Cw3- or Cw4-transfected 721.221 lymphoblastoid cell line, triggered gammadelta T cell apoptosis, interacting with the specific receptors CD158j/KIR2DS2 or CD158 h/KIR2DS1, respectively, also known as activating isoforms of killer Ig-like receptors (KIR) [10].

Anatomical context of KIR2DS2

• First, we show using plastic-immobilized CD158b mAb that the activating KIR2DS2 is stimulated, resulting in NK cell division and degranulation [11].
• Under incubation conditions used previously to document in vitro adherence of other diarrheagenic E. coli, only the one type-1 fimbriated E. coli O157:H7 strain, designated CL-49, adhered to isolated human and rabbit epithelial cells [12].
• Adherence of vero cytotoxin-producing Escherichia coli serotype O157:H7 to isolated epithelial cells and brush border membranes in vitro: role of type 1 fimbriae (pili) as a bacterial adhesin expressed by strain CL-49 [12].

Associations of KIR2DS2 with chemical compounds

• Substitution of tyrosine 45 with the phenylalanine conserved in other KIR was sufficient to permit specific binding of KIR2DS2 to HLA-C [13].
• We also found KIR2DS2 with its presumed C1 group ligand less prevalent in TB patients than in the control group, but this result lost significance after correction [14].

Other interactions of KIR2DS2

• One of these receptors (KIR2DS2) is closely related in sequence to KIR2DL2 [13].
• The KIR2DS2 gene was significantly enriched among patients with rheumatoid vasculitis compared with normal individuals (odds ratio 5.56, P = 0.001) and patients with RA but no vasculitis (odds ratio 7.96, P = 0.001) [4].
• In clones that lacked expression of KARAP/DAP12, stimulation of KIR2DS2 did not induce cytotoxicity [15].
• However, KIR2DS2 did augment suboptimal TCR stimulation, leading to enhanced IFN-gamma production [15].

Analytical, diagnostic and therapeutic context of KIR2DS2

• In contrast, the presence of KIR2DS2 (n = 13/25 donors) was associated with decreased probability of overall survival (0% vs 92%, P = .04) and disease-free survival (0% vs 92%, P = .046) [8].

References