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Genetic control of human NK cell rep...

Shilling, Heather Gwendolyn.

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Genetic control of human NK cell repertoire.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Genetic control of human NK cell repertoire./
作者:	Shilling, Heather Gwendolyn.
面頁冊數:	87 p.
附註:	Adviser: Peter Parham.
Contained By:	Dissertation Abstracts International63-01B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3040066
ISBN:	0493533915

Genetic control of human NK cell repertoire.
Shilling, Heather Gwendolyn.

Genetic control of human NK cell repertoire. - 87 p.

Adviser: Peter Parham.

Thesis (Ph.D.)--Stanford University, 2002.

Natural killer (NK) cells express cell surface receptors that recognize polymorphic determinants of major histocompatibility complex (MHC) molecules and inhibit NK cell activity. In humans, differential expression of killer cell Ig-like receptors (KIR) and CD94:NKG2 by NK cells creates diverse repertoires, each cell having an inhibitory receptor for autologous class I human leukocyte antigens (HLA). This apparent adaptation of NK cell receptor repertoire to MHC environment has been difficult to reconcile, however, with evidence that KIR expression is controlled by <italic>non-HLA</italic> genetic elements.

ISBN: 0493533915Subjects--Topical Terms:

1017686
Biology, Cell.

Genetic control of human NK cell repertoire.
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500 $a Source: Dissertation Abstracts International, Volume: 63-01, Section: B, page: 0168.
502 $a Thesis (Ph.D.)--Stanford University, 2002.
520 $a Natural killer (NK) cells express cell surface receptors that recognize polymorphic determinants of major histocompatibility complex (MHC) molecules and inhibit NK cell activity. In humans, differential expression of killer cell Ig-like receptors (KIR) and CD94:NKG2 by NK cells creates diverse repertoires, each cell having an inhibitory receptor for autologous class I human leukocyte antigens (HLA). This apparent adaptation of NK cell receptor repertoire to MHC environment has been difficult to reconcile, however, with evidence that KIR expression is controlled by <italic>non-HLA</italic> genetic elements.
520 $a <italic>KIR</italic> population diversity makes the <italic>KIR</italic> locus itself a candidate for the <italic>non-HLA</italic> genes controlling KIR phenotype. To examine how allelic polymorphism diversifies haplotypes having matching sets of <italic>KIR</italic> genes, PCR subtyping methods were designed to discriminate alleles of <italic>KIR2DL1</italic>, <italic> 2DL3</italic>, <italic>3DL1</italic>, and <italic>3DL2</italic>. These were applied to 143 individuals from 34 families to define 98 parental <italic> KIR</italic> haplotypes. Among these were <italic>A</italic> group haplotypes having 22 different combinations of <italic>2DL1</italic>, <italic>2DL3</italic>, <italic> 3DL1</italic>, and <italic>3DL2</italic> alleles, and 15 distinct <italic> B</italic> group haplotypes involving 9 different sets of <italic>KIR</italic> genes. The synergistic combination of allelic polymorphism and variable gene content individualize <italic>KIR</italic> genotype such that unrelated individuals are rarely <italic>KIR</italic>-matched.
520 $a Using a new method for measuring KIR repertoire difference that integrates multiple flow cytometry parameters, the hypothesis that <italic>KIR</italic> genotype controls KIR phenotype was tested by: (1) comparing KIR and CD94:NKG2 expression in healthy siblings pairs of known <italic>HLA</italic> and <italic>KIR</italic> type, and (2) by following KIR repertoire reconstitution after allogeneic, <italic>HLA</italic>-matched stem cell transplantation. Correlating repertoire differences with <italic>KIR</italic> and <italic> HLA</italic> genotype for 85 sibling pairs revealed the dominant influence of <italic>KIR</italic> genotype; <italic>HLA</italic> having a subtle, modulating effect on relative frequencies of KIR-expressing cells. <italic>HLA</italic> and <italic>KIR</italic> genotype also influenced CD94:NKG2A expression, and frequencies of CD94:NKG2A and KIR-expressing cells were inversely correlated. After <italic>HLA</italic>-matched transplantation, reconstituted KIR repertoires either recapitulated that of the donor, or showed a general depression in KIR expression. Human NK cell repertoires appear genetically predetermined, defined by combinations of variable <italic>KIR</italic> and class I <italic> HLA</italic> genes and conserved <italic>CD94:NKG2</italic> genes.
590 $a School code: 0212.
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