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  • 1
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We previously isolated a series of cDNA clones designated NKG2-A, B, C, and D from a human natural killer (NK) cell library. These transcripts encode a family of type II integral membrane proteins having an extracellular Ca2+-dependent lectin domain. The predicted peptides share structural similarities and amino acid sequence similarity with known receptor molecules. In this report, the genomic organization and mRNA expression of each of the genes were studied by using transcript-specific probes. Southern blot experiments reveal that the probes cross-hybridize with a maximum of five genes at high stringency. By probing a Southern blot prepared from a series of hamster/human hybrid somatic cell lines, we demonstrated that all of the hybridizing fragments occur on human chromosome 12. No gene rearrangement and little restriction fragment length polymorphism (RFLP) was observed with these probes. mRNA expression of the NKG2 genes occured in NK cells and some T cells but not in other hematopoietic cell types or in other tissues tested. Each of the transcripts occurred in all three of the NK cell lines tested: however, the genes were differentially regulated in T cells. NKG2-D was expressed in nine of fourteen T-cell clones or lines in the panel, whereas NKG2-A/B was expressed in three and NKG2-C was expressed in only one. Expression of each of the transcripts was upregulated following T-cell growth factor (TCGF)-induced activation of a cloned NK cell. The limited distribution of these proteins and their sequence similarity with known receptor molecules suggest that they may function as receptors of human NK cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We reported previously the isolation of a cDNA clone, designated NKG5, encoding a secreted protein that is expressed only in natural killer and T cells and is strongly upregulated upon cell activation. In this report we have isolated the NKG5 gene from a human placental genomic library and sequenced the gene and two kilobases of 5'-flanking DNA. Comparison with the cDNA sequence reveals that the NKG5 gene consists of five exons and four introns. Intron 1 contains a DNA segment that was reported to occur as an exon in 519, a closely related cDNA clone that was isolated from a T-cell library. This result indicates that NKG5 and 519 are alternative splicing products of a single gene. The 5′-flanking region of the NKG5 gene was analyzed for homology with the promoter regions of cytokines and other activation-induced genes showing lymphocyte-specific expression. Several segments displaying sequence similarity were identified. We also identified numerous sequence elements that have strong similarity to known binding sites for transcriptional regulatory proteins including T-cell-specific and activation-specific regulatory factors. These findings are consistent with the cell-specific expression and the tight regulatory control that is observed for the NKG5 gene.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-198X
    Keywords: Donor antigen-specific hyporeactivity ; Allogeneic microchimerism ; Kidney recipients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Our previous studies indicate donor antigenspecific hyporeactivity is a useful marker for identifying solid organ transplant recipients at low risk for immunological complications; the hyporeactive subgroup experiences a lower incidence of chronic rejection. One purpose of the current study was to determine whether hyporeactivity could be identified in pediatric kidney recipients and whether it correlated with improved graft outcome. Of 18 pediatric kidney recipients tested, 6 (33%) had developed donor antigen-specific hyporeactivity. All 18 experienced good graft outcome. Second, we determined whether donor antigen-specific hyporeactivity correlates with peripheral blood microchimerism and outcome in adult kidney recipients. Our previous studies of lung recipients demonstrated development of obliterative bronchiolitis in recipients with microchimerism who remain responsive, but not in recipients who had become hyporesponsive to donor antigen. Preliminary results in our current study of 23 adult kidney recipients indicate microchimerism for 6 (26%): 4 hyporesponsive and 2 responsive to donor antigen. Microchimerism was not detected for 17 recipients: 6 hyporesponsive and 11 responsive to donor antigen. One hyporesponsive/chimeric patient and 4 recipients negative for both parameters have been diagnosed with biopsy-proven chronic rejection. In summary, both hyporeactivity and chimerism are found at a higher frequency in lung than kidney recipients. Unlike lung recipients, not all hyporesponsive kidney recipients had peripheral blood chimerism. Additional numbers are needed to determine if microchimerism correlates with donor antigen-specific hyporeactivity or graft outcome.
    Type of Medium: Electronic Resource
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