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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.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Genetic control of human NK cell repertoire./
Author:	Shilling, Heather Gwendolyn.
Description:	87 p.
Notes:	Adviser: Peter Parham.
Contained By:	Dissertation Abstracts International63-01B.
Subject:	Biology, Cell. -
Online resource:	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.
LDR:03835nam 2200301 a 45 001 927676
005 20110425
008 110425s2002 eng d
020 $a 0493533915
035 $a (UnM)AAI3040066
035 $a AAI3040066
040 $a UnM $c UnM
100 1 $a Shilling, Heather Gwendolyn. $3 1251240
245 1 0 $a Genetic control of human NK cell repertoire.
300 $a 87 p.
500 $a Adviser: Peter Parham.
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.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0379
690 $a 0982
710 2 0 $a Stanford University. $3 754827
773 0 $t Dissertation Abstracts International $g 63-01B.
790 $a 0212
790 1 0 $a Parham, Peter, $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3040066