L L Lanier

..This may contribute to the phenotype and progression of this disease...

..Phosphorylated DAP12 peptides bind ZAP-70 and Syk protein tyrosine kinases, suggesting that the activation pathway is similar to that of the T- and B-cell antigen receptors...

..Recent studies suggest these inhibitory NK cell receptors are members of a larger superfamily containing ITIM sequences, the inhibitory receptor superfamily (IRS)...

..These results provide a molecular basis for the assembly of NK cell receptors for MHC class I involved in cellular activation and inhibition...

..Here we review the membrane receptors on human NK cells that are known to initiate cell-mediated cytotoxicity and demonstrate regulation of these responses by the killer cell inhibitory (KIR) receptors...

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..Genes encoding the murine and human NK-cell receptors have been cloned, and studies of their structure, function and expression are progressing rapidly, as reviewed here by Lewis Lanier and Joseph Phillips...

..These findings suggest the existence of human inhibitory MHC class I receptors of the immunoglobulin and C-type lectin superfamilies and indicate overlap in ligand specificity...

..Structural heterogeneity in the NKG2 gene family and the formation of heterodimers with CD94 provides for the creation of a diverse NK cell repertoire...

..Stimulation of transfectants with Abs recognizing either Ly-49D or Ly-49H results in cellular activation, as assessed by induction of tyrosine phosphorylation of multiple cellular substrates...

..Mouse SLAM also associates with the recently described human SLAM-associated protein. These studies may provide new insights into the regulation of Th1 responses...

..These results suggest that the phenotype of XLP may result from perturbed signaling not only through SLAM, but also other cell surface molecules that utilize SAP as a signaling adaptor protein...

..Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors...

..Crosslinking of MDL-1/DAP12 complexes in J774 mouse macrophage cells resulted in calcium mobilization. These findings suggest that signaling via MDL-1/DAP12 complexes may constitute a significant activation pathway in myeloid cells...

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..Our findings demonstrate that NKR-P1A is a human homologue of the rodent NKR-P1 genes and suggest that this molecule may be involved in NK cell function...

..This indicates that LAIR-1 provides a mechanism of regulation of effector T cells and may play a role in the inhibition of unwanted bystander responses mediated by Ag-specific T cells...

..In addition, DNAM-1 is a tyrosine-phosphorylated signal-transducing molecule that participates in primary adhesion during cytotoxic T lymphocyte (CTL)-mediated cytotoxicity...

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..Taken together, these results suggest that CD148 is an important phosphatase involved in negatively regulating the proximal signaling events during activation of Ag-specific T cells...

..These results indicate that expression of CD3 gamma delta epsilon subunits is not restricted to T lymphocytes and supports the possibility that NK and T cells may be derived from common origins...

..These findings demonstrate the existence of NK cell receptors involved in the recognition of HLA-B and imply the presence of multiple receptors for MHC on an individual NK clone...

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..These studies demonstrate that a single NK cell clone may possess multiple structurally distinct receptors for different polymorphic HLA class I molecules that function independently...

..An unexpected feature of CD94 is the essential absence of a cytoplasmic domain, implying that association with other receptors may be necessary for the function of this molecule...

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..Thus, newly generated NKT cells may possess the potent ability to develop into IL-4(+)IFN-gamma(-) NKT2 cells in response to appropriate stimuli and may thereafter acquire the tendency to produce both IL-4 and IFN-gamma...

..CD148-induced proliferation was significantly greater for CD8+ T cells than for CD4+ T cells. Thus, CD148 is a receptor-type protein tyrosine phosphatase involved in the activation of T lymphocytes...

..These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses...

..Therefore, the role of CD80 and CD86 in an immune response may be determined primarily by their differential expression on APC...

..These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation...

..These results suggest that the primary role of HLA-G may be the modulation of myelomonocytic cell behavior in pregnancy...

..A better understanding about how targets signal their distress, which renders them susceptible to natural killer (NK)-cell attack, will help to define the role of NK cells in antimicrobial and antitumor immunity and transplantation...

..These results demonstrate the rapid evolution of NK cell receptor systems and imply that "catching up" with class I is not the only force driving this evolution...

..Because of these differences, the first donor has subpopulations of NK cells that kill cells of the second donor, whereas the NK cells of the second donor are universally tolerant of cells from the first donor...

..These results demonstrate that the activating KIR2DS2 can function on cells co-expressing the inhibitory KIR2DL2 and/or KIR2DL3, indicating the potential for independent function of activating KIR with natural ligand...

..6 cM interval flanked by the genetic markers D12S397 and D12S89. The physical distance spanned by the NK gene complex in humans ranges between 0.7 and 2.4 megabases...

..No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP...

..In Northern blot analysis, DAP12 transcripts were detected in spleen, liver, thymus, and lymph node. DAP12 transcripts are expressed not only in PBLs, but also in granulocytes, macrophages, and monocytes...

..Cytotoxicity mediated by the DX5(+) NK cells was dramatically higher as compared with DX5(-) NK cells. Therefore, DX5 mAb recognizes CD49b and can be used to define functionally distinct subsets of NK cells...

..In addition, cross-linking of LFA-1 induces tyrosine phosphorylation of DNAM-1, for which the Fyn protein tyrosine kinase is responsible. These results indicate that DNAM-1 is involved in the LFA-1-mediated intracellular signals...

..Remarkably, among 55 T cell clones sharing the same TCR alpha beta rearrangement 18 different KIR phenotypes were seen, suggesting that KIR expression was initiated subsequently to TCR rearrangement...

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..Group B comprises more noninhibitory KIR genes and contains at least one additional gene not represented in group A. The KIR locus therefore appears to be polygenic and polymorphic within the human population...

..Since Ly-49A may shift the signaling threshold of TCR-induced triggering, inducible expression of Ly-49A may regulate peripheral memory/activated T cells by raising the threshold for T cell reactivation...

..While reviewing these attack-counterattack measures, this chapter points to the central role that recognition of the MCMV-infected cells by NK cells plays in host resistance to infection...

..Varying affinities of MICA alleles for NKG2D may affect thresholds of NK-cell triggering and T-cell modulation...

..The distinct thermodynamic profiles provide insights into the different molecular mechanisms of the binding interactions...

..Therefore, NK cells are able to reject a tumor expressing RAE-1 molecules, despite expression of self MHC class I on the tumor, demonstrating the potential for NK cells to participate in immunity against class I-bearing malignancies...

..Our studies define TREM-2 as a receptor family in mouse macrophages and demonstrate the capacity of these receptors to activate macrophage function through DAP12...

..These studies identify a family of ligands for the activating NKG2D receptor on NK and T cells, which may play an important role in innate and adaptive immunity...

..Conversion of Phe to Ser in CD16-II permits expression of a PI-glycan-anchored glycoprotein, whereas conversion of Ser to Phe in CD16-I prevents PI-glycan linkage...

..These data indicate that NKG2-A and NKG2-C deliver, respectively, inhibitory and activating transmembrane signals in NK cells...

..These results suggest sequential roles for Lck and SHP-1 in the inhibition of PTK following MHC recognition by NK cells...

..These findings indicate that B70 is a second ligand for CD28 and CTLA-4 and may play an important role for costimulation of T cells in a primary immune response...

..Fc alpha/microR also mediated primary B lymphocyte endocytosis of IgM-coated Staphylococcus aureus. Thus, Fc alpha/microR is involved in the primary stages of the immune response to microbes...

..Moreover, we describe how viruses and cancer have developed strategies to evade this recognition pathway...

..Collectively, these studies indicate that homophilic N-CAM interactions probably do not mediate a major role in the cytolytic interaction between NK cells and N-CAM+ tumor cell targets...

..RT-PCR analysis reveals that pig NKG2D transcripts are expressed in PBLs, NK cells, macrophages, and monocytes. When transiently transfected into COS-7 cells, pig NKG2D requires DAP10 for cell surface expression...

..These results represent the first definitive evidence of a common T/NK cell progenitor in the human fetal thymus and delineate the point in thymocyte differentiation where T and NK cells diverge...

..Thus, Ets-1 defines a novel transcriptional pathway that is required for the development of the NK cell lineage in mice...

..We propose that LAIR-1--Ep-CAM interaction may contribute to mucosal tolerance and that LAIR-2 possibly modulates this function...

..Here, we review the emerging evidence that natural killer cells have an important role in vivo in immune defence...

..Three distinct phenotypes were presented: (1) Lym 7.2+ Lym 7.3+; (2) Lym 7.2+ Lym 7.3-; and (3) Lym 7.2- Lym 7.3-. Genetic studies suggested both specificities were encoded by a single locus...

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..Most of these cells had a V delta gene segment not previously described (V delta 3), and the delta chain junctional sequences formed a discrete subpopulation compared with those previously reported...